{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T04:09:01Z","timestamp":1792382941565,"version":"4.4.0"},"reference-count":207,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T00:00:00Z","timestamp":1674691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>The chronic kidney disease-mineral bone disorder (CKD-MBD) is a complex multi-component syndrome occurring during kidney disease and its progression. Here, we update progress in the components of the syndrome, and synthesize recent investigations, which suggest a potential mechanism of the bone-vascular paradox. The discovery that calcified arteries in chronic kidney disease inhibit bone remodeling lead to the identification of factors produced by the vasculature that inhibit the skeleton, thus providing a potential explanation for the bone-vascular paradox. Among the factors produced by calcifying arteries, sclerostin secretion is especially enlightening. Sclerostin is a potent inhibitor of bone remodeling and an osteocyte specific protein. Its production by the vasculature in chronic kidney disease identifies the key role of vascular cell osteoblastic\/osteocytic transdifferentiation in vascular calcification and renal osteodystrophy. Subsequent studies showing that inhibition of sclerostin activity by a monoclonal antibody improved bone remodeling as expected, but stimulated vascular calcification, demonstrate that vascular sclerostin functions to brake the Wnt stimulation of the calcification milieu. Thus, the target of therapy in the chronic kidney disease-mineral bone disorder is not inhibition of sclerostin function, which would intensify vascular calcification. Rather, decreasing sclerostin production by decreasing the vascular osteoblastic\/osteocytic transdifferentiation is the goal. This might decrease vascular calcification, decrease vascular stiffness, decrease cardiac hypertrophy, decrease sclerostin production, reduce serum sclerostin and improve skeletal remodeling. Thus, the therapeutic target of the chronic kidney disease-mineral bone disorder may be vascular osteoblastic transdifferentiation, and sclerostin levels may be a useful biomarker for the diagnosis of the chronic kidney disease-mineral bone disorder and the progress of its therapy.<\/jats:p>","DOI":"10.3389\/fphys.2023.1120308","type":"journal-article","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T01:22:48Z","timestamp":1674696168000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Updates in the chronic kidney disease-mineral bone disorder show the role of osteocytic proteins, a potential mechanism of the bone\u2014Vascular paradox, a therapeutic target, and a biomarker"],"prefix":"10.3389","volume":"14","author":[{"given":"Matthew J.","family":"Williams","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah C.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Joseph","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith A.","family":"Hruska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"R592","DOI":"10.1016\/s0960-9822(01)00360-8","article-title":"Wnt signalling: Antagonistic dickkopfs","volume":"11","author":"Aaron","year":"2001","journal-title":"Curr. Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1681\/ASN.2008040349","article-title":"Association of serum phosphate with vascular and valvular calcification in moderate CKD","volume":"20","author":"Adeney","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/81664","article-title":"Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23","volume":"26","year":"2000","journal-title":"Nat. Genet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1038\/ki.2011.423","article-title":"Decreased renal \u03b1-Klotho expression in early diabetic nephropathy in humans and mice and its possible role in urinary calcium excretion","volume":"81","author":"Asai","year":"2012","journal-title":"Kidney Int."},{"key":"B5","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1038\/35083081","article-title":"Novel mechanism of Wnt signalling inhibition mediated byDickkopf-1 interaction with LRP6\/Arrow","volume":"3","author":"Bafico","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1186\/s12967-017-1190-z","article-title":"A novel role of cellular interactions in vascular calcification","volume":"15","author":"Bardeesi","year":"2017","journal-title":"J. Transl. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1159\/000321520","article-title":"Prognostic implication of plasma osteopontin levels in patients with chronic kidney disease","volume":"117","author":"Barreto","year":"2011","journal-title":"Nephron Clin. Pract."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e0176411","DOI":"10.1371\/journal.pone.0176411","article-title":"Circulating levels of sclerostin but not DKK1 associate with laboratory parameters of CKD-MBD","volume":"12","author":"Behets","year":"2017","journal-title":"PLOS ONE"},{"key":"B9","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1007\/s00774-018-0919-y","article-title":"High calcium, phosphate and calcitriol supplementation leads to an osteocyte-like phenotype in calcified vessels and bone mineralisation defect in uremic rats","volume":"37","author":"Bisson","year":"2019","journal-title":"J. Bone Mineral Metabolism"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2132","DOI":"10.2215\/CJN.04260413","article-title":"CKD\u2013Mineral and bone disorder and risk of death and cardiovascular hospitalization in patients on hemodialysis","volume":"8","author":"Block","year":"2013","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2208","DOI":"10.1097\/01.ASN.0000133041.27682.A2","article-title":"Mineral metabolism, mortality, and morbidity in maintenance hemodialysis","volume":"15","author":"Block","year":"2004","journal-title":"J. Am. Soc. Nephrol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e81710","DOI":"10.1371\/journal.pone.0081710","article-title":"Mutational analysis of sclerostin shows importance of the flexible loop and the cystine-knot for wnt-signaling inhibition","volume":"8","author":"Boschert","year":"2013","journal-title":"PLOS ONE"},{"key":"B13","doi-asserted-by":"publisher","first-page":"eaay6570","DOI":"10.1126\/scitranslmed.aay6570","article-title":"Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics","volume":"12","author":"Bovijn","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.yexcr.2016.06.007","article-title":"WNT\/\u03b2-catenin signaling promotes VSMCs to osteogenic transdifferentiation and calcification through directly modulating Runx2 gene expression","volume":"345","author":"Cai","year":"2016","journal-title":"Exp. Cell Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1046\/j.1523-1755.2001.00781.x","article-title":"Fibroblast growth factor receptors and their ligands in the adult rat kidney","volume":"60","author":"Cancilla","year":"2001","journal-title":"Kidney Int."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2589","DOI":"10.3390\/nu14132589","article-title":"Vitamin D treatment prevents uremia-induced reductions in aortic microRNA-145 attenuating osteogenic differentiation despite hyperphosphatemia","volume":"14","author":"Carrillo-L\u00f3pez","year":"2022","journal-title":"Nutrients"},{"key":"B17","doi-asserted-by":"publisher","first-page":"877","DOI":"10.2215\/CJN.06550810","article-title":"Sclerostin and dickkopf-1 in renal osteodystrophy","volume":"6","author":"Cejka","year":"2011","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1080\/15548627.2019.1704117","article-title":"TGFB-INHB\/activin signaling regulates age-dependent autophagy and cardiac health through inhibition of MTORC2","volume":"16","author":"Chang","year":"2020","journal-title":"Autophagy"},{"key":"B19","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1038\/nature25451","article-title":"\u03b1-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling","volume":"553","author":"Chen","year":"2018","journal-title":"Nature"},{"key":"B20","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/j.kint.2017.07.019","article-title":"Matrix vesicles induce calcification of recipient vascular smooth muscle cells through multiple signaling pathways","volume":"93","author":"Chen","year":"2018","journal-title":"Kidney Int."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1093\/ndt\/gfh125","article-title":"Determinants of progressive vascular calcification in haemodialysis patients","volume":"19","author":"Chertow","year":"2004","journal-title":"Nephrol. Dial. Transplant."},{"key":"B22","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1097\/mol.0b013e32831ef234","article-title":"Metabolic abnormalities in chronic kidney disease that contribute to cardiovascular disease, and nutritional initiatives that may diminish the risk","volume":"20","author":"Chmielewski","year":"2009","journal-title":"Curr. Opin. Lipidol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"3221","DOI":"10.1210\/jc.2013-1521","article-title":"Sclerostin: Another vascular calcification inhibitor?","volume":"98","author":"Claes","year":"2013","journal-title":"J. Clin. Endocrinol. Metabolism"},{"key":"B24","doi-asserted-by":"publisher","first-page":"14092","DOI":"10.1073\/pnas.1207188109","article-title":"Targeted deletion of Sost distal enhancer increases bone formation and bone mass","volume":"109","author":"Collette","year":"2012","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1056\/NEJMoa1607948","article-title":"Romosozumab treatment in postmenopausal women with osteoporosis","volume":"375","author":"Cosman","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"c187","DOI":"10.1159\/000317198","article-title":"The effects of vitamin D therapy on left ventricular structure and function \u2013 are these the underlying explanations for improved CKD patient survival?","volume":"116","author":"Covic","year":"2010","journal-title":"Nephron Clin. Pract."},{"key":"B27","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1159\/000124863","article-title":"The circulating inactive form of matrix gla protein (ucMGP) as a biomarker for cardiovascular calcification","volume":"45","author":"Cranenburg","year":"2008","journal-title":"J. Vasc. Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/j.csbj.2019.06.015","article-title":"Early vascular ageing and cellular senescence in chronic kidney disease","volume":"17","author":"Dai","year":"2019","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1038\/ki.2012.482","article-title":"Phosphate-induced autophagy counteracts vascular calcification by reducing matrix vesicle release","volume":"83","author":"Dai","year":"2013","journal-title":"Kidney Int."},{"key":"B30","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1002\/jbm4.10117","article-title":"Rethinking bone disease in kidney disease","volume":"2","author":"Damasiewicz","year":"2018","journal-title":"JBMR Plus"},{"key":"B31","doi-asserted-by":"publisher","first-page":"4469","DOI":"10.1210\/en.2013-1627","article-title":"Calcium regulates FGF-23 expression in bone","volume":"154","author":"David","year":"2013","journal-title":"Endocrinology"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1097\/01.asn.0000068404.57780.dd","article-title":"BMP-7 is an efficacious treatment of vascular calcification in a murine model of atherosclerosis and chronic renal failure","volume":"14","author":"Davies","year":"2003","journal-title":"J. Am. Soc. Nephrol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1002\/jbmr.4503","article-title":"Sclerostin protects against vascular calcification development in mice","volume":"37","author":"De Mar\u00e9","year":"2022","journal-title":"J. Bone Mineral Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2510","DOI":"10.1093\/ndt\/gft234","article-title":"Disturbances of wnt\/\u03b2-catenin pathway and energy metabolism in early CKD: Effect of phosphate binders","volume":"28","author":"de Oliveira","year":"2013","journal-title":"Nephrol. Dial. Transpl."},{"key":"B35","doi-asserted-by":"publisher","first-page":"2029","DOI":"10.1161\/01.cir.92.8.2029","article-title":"A skeleton in the atherosclerosis closet","volume":"92","author":"Demer","year":"1995","journal-title":"Circulation"},{"key":"B36","doi-asserted-by":"publisher","first-page":"487","DOI":"10.2215\/CJN.03820411","article-title":"Independent study investigators mortality in kidney disease patients treated with phosphate binders: A randomized study","volume":"7","author":"Di Iorio","year":"2012","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1159\/000435838","article-title":"Left ventricular hypertrophy in chronic kidney disease patients: From pathophysiology to treatment","volume":"5","author":"Di Lullo","year":"2015","journal-title":"Cardiorenal Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"8655","DOI":"10.1074\/jbc.M110.174037","article-title":"Klotho inhibits transforming growth factor-beta1 (TGF-beta1) signaling and suppresses renal fibrosis and cancer metastasis in mice","volume":"286","author":"Doi","year":"2011","journal-title":"J. Biol. Chem."},{"key":"B39","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1093\/cvr\/cvy010","article-title":"Role of smooth muscle cells in vascular calcification: Implications in atherosclerosis and arterial stiffness","volume":"114","author":"Durham","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.kint.2017.08.036","article-title":"Not all vascular smooth muscle cell exosomes calcify equally in chronic kidney disease","volume":"93","author":"Dusso","year":"2018","journal-title":"Kidney Int."},{"key":"B41","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1038\/nrneph.2016.54","article-title":"Developmental signalling pathways in renal fibrosis: The roles of notch, Wnt and hedgehog","volume":"12","author":"Edeling","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1016\/j.ekir.2022.02.022","article-title":"Low turnover renal osteodystrophy with abnormal bone quality and vascular calcification in patients with mild-to-moderate CKD","volume":"7","author":"El-Husseini","year":"2022","journal-title":"Kidney Int. Rep."},{"key":"B43","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/ki.2015.156","article-title":"Sclerostin and DKK1: New players in renal bone and vascular disease","volume":"88","author":"Evenepoel","year":"2015","journal-title":"Kidney Int."},{"key":"B44","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1053\/j.ackd.2019.09.006","article-title":"Bone-vascular Axis in chronic kidney disease","volume":"26","author":"Evenepoel","year":"2019","journal-title":"Adv. Chronic Kidney Dis."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1760","DOI":"10.1681\/ASN.2013080818","article-title":"CKD-Induced wingless\/integration1 inhibitors and phosphorus cause the CKD-mineral and bone disorder","volume":"25","author":"Fang","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1038\/ki.2013.271","article-title":"Early chronic kidney disease-mineral bone disorder stimulates vascular calcification","volume":"85","author":"Fang","year":"2014","journal-title":"Kidney Int."},{"key":"B47","doi-asserted-by":"publisher","first-page":"4393","DOI":"10.1172\/JCI46122","article-title":"FGF23 induces left ventricular hypertrophy","volume":"121","author":"Faul","year":"2011","journal-title":"J. Clin. Invest."},{"key":"B48","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1007\/s11255-019-02290-3","article-title":"Sclerostin: A new biomarker of CKD\u2013MBD","volume":"52","author":"Figurek","year":"2020","journal-title":"Int. Urology Nephrol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"2600","DOI":"10.1681\/ASN.2006080936","article-title":"Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disease: The mild to moderate kidney disease (MMKD) study","volume":"18","author":"Fliser","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"S112","DOI":"10.1053\/ajkd.1998.v32.pm9820470","article-title":"Clinical epidemiology of cardiovascular disease in chronic renal disease","volume":"32","author":"Foley","year":"1998","journal-title":"Am. J. Kidney Dis."},{"key":"B51","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1002\/jcb.10369","article-title":"Regulation of the osteoblast-specific transcription factor, Runx2: Responsiveness to multiple signal transduction pathways","volume":"88","author":"Franceschi","year":"2003","journal-title":"J. Cell. Biochem."},{"key":"B52","doi-asserted-by":"publisher","first-page":"33132","DOI":"10.1074\/jbc.M500608200","article-title":"Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression","volume":"280","author":"Gaur","year":"2005","journal-title":"J. Biol. Chem."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1172\/JCI116755","article-title":"Osteopontin is elevated during neointima formation in rat arteries and is a novel component of human atherosclerotic plaques","volume":"92","author":"Giachelli","year":"1993","journal-title":"J. Clin. Investigation"},{"key":"B54","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1161\/01.RES.0000161997.24797.c0","article-title":"Regulation of vascular calcification: Roles of phosphate and osteopontin","volume":"96","author":"Giachelli","year":"2005","journal-title":"Circulation Res."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1056\/NEJMoa041031","article-title":"Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization","volume":"351","author":"Go","year":"2004","journal-title":"New Engl. J. Med."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1161\/CIRCRESAHA.113.300937","article-title":"MicroRNA in cardiovascular calcification: Focus on targets and extracellular vesicle delivery mechanisms","volume":"112","author":"Goettsch","year":"2013","journal-title":"Circ. Res."},{"key":"B57","doi-asserted-by":"publisher","first-page":"e187","DOI":"10.1161\/ATVBAHA.122.317635","article-title":"Role of sclerostin in cardiovascular disease","volume":"42","author":"Golledge","year":"2022","journal-title":"Arteriosclerosis, Thrombosis, Vasc. Biol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/s0092-8674(01)00571-2","article-title":"LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development","volume":"107","author":"Gong","year":"2001","journal-title":"Cell"},{"key":"B59","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1016\/j.cmet.2015.09.002","article-title":"Activation of cardiac fibroblast growth factor receptor 4 causes left ventricular hypertrophy","volume":"22","author":"Grabner","year":"2015","journal-title":"Cell Metab."},{"key":"B60","first-page":"774A","article-title":"Wnt pathway inhibition: Another actor in CKD-MBD pathophysiology?","volume":"21","author":"Graciolli","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1016\/j.kint.2016.12.029","article-title":"The complexity of chronic kidney disease-mineral and bone disorder across stages of chronic kidney disease","volume":"91","author":"Graciolli","year":"2017","journal-title":"Kidney Int."},{"key":"B62","doi-asserted-by":"publisher","first-page":"2545","DOI":"10.1161\/CIRCULATIONAHA.108.844506","article-title":"Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease","volume":"119","author":"Gutierrez","year":"2009","journal-title":"Circulation"},{"key":"B63","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1056\/NEJMoa0706130","article-title":"Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis","volume":"359","author":"Gutierrez","year":"2008","journal-title":"New Engl. J. Med."},{"key":"B64","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1161\/ATVBAHA.113.303062","article-title":"Plasma parathyroid hormone is associated with subclinical and clinical atherosclerotic disease in 2 community-based cohorts","volume":"34","author":"Hagstr\u00f6m","year":"2014","journal-title":"Arteriosclerosis, Thrombosis, Vasc. Biol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1161\/CIRCULATIONAHA.119.044801","article-title":"A novel treatment for vascular calcification in patients with dialysis-dependent chronic kidney disease","volume":"141","author":"Hedayati","year":"2020","journal-title":"Circulation"},{"key":"B66","doi-asserted-by":"publisher","first-page":"3986","DOI":"10.1016\/j.bpj.2010.10.030","article-title":"Fetuin-A is a mineral carrier protein: Small angle neutron scattering provides new insight on fetuin-A controlled calcification inhibition","volume":"99","author":"Heiss","year":"2010","journal-title":"Biophysical J."},{"key":"B67","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1161\/ATVBAHA.117.309513","article-title":"Oligogalacturonic acid inhibits vascular calcification by two mechanisms: Inhibition of vascular smooth muscle cell osteogenic conversion and interaction with collagen","volume":"37","author":"Hodroge","year":"2017","journal-title":"Arteriosclerosis, Thrombosis, Vasc. Biol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"eabe8497","DOI":"10.1126\/scitranslmed.abe8497","article-title":"Comment on \"Evaluating the cardiovascular safety of sclerostin inhibition using evidence from meta-analysis of clinical trials and human genetics","volume":"13","author":"H\u00f3lm","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"B69","article-title":"CKD-MBD syndrome: CKD produced disorders in Skeletal, Vascular, and cardiac tissues and mineral metabolism","volume-title":"DeGroot\u2019s endocrinology","author":"Hruska","year":"2022"},{"key":"B70","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.bone.2017.01.023","article-title":"The chronic kidney disease \u2014 mineral bone disorder (CKD-MBD): Advances in pathophysiology","volume":"100","author":"Hruska","year":"2017","journal-title":"Bone"},{"key":"B71","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1159\/000346778","article-title":"Klotho and chronic kidney disease","volume":"180","author":"Hu","year":"2013","journal-title":"Contrib. Nephrol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1016\/j.kint.2016.10.034","article-title":"Recombinant \u03b1-Klotho may be prophylactic and therapeutic for acute to chronic kidney disease progression and uremic cardiomyopathy","volume":"91","author":"Hu","year":"2017","journal-title":"Kidney Int."},{"key":"B73","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1681\/ASN.2014101030","article-title":"Renal production, uptake, and handling of circulating \u03b1Klotho","volume":"27","author":"Hu","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1681\/ASN.2009121311","article-title":"Klotho deficiency causes vascular calcification in chronic kidney disease","volume":"22","author":"Hu","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.febslet.2004.03.090","article-title":"Secreted klotho protein in sera and CSF: Implication for post-translational cleavage in release of klotho protein from cell membrane","volume":"565","author":"Imura","year":"2004","journal-title":"FEBS Lett."},{"key":"B76","doi-asserted-by":"publisher","first-page":"2482","DOI":"10.1056\/NEJMoa1205624","article-title":"Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis","volume":"367","author":"Investigators","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"B77","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1681\/ASN.2017070772","article-title":"Longitudinal FGF23 trajectories and mortality in patients with CKD","volume":"29","author":"Isakova","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1038\/ki.2011.47","article-title":"Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease","volume":"79","author":"Isakova","year":"2011","journal-title":"Kidney Int."},{"key":"B79","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1053\/j.ajkd.2022.03.006","article-title":"A klotho-derived peptide as a possible novel drug to prevent kidney fibrosis","volume":"80","author":"Isakova","year":"2022","journal-title":"Am. J. Kidney Dis."},{"key":"B80","doi-asserted-by":"publisher","first-page":"609","DOI":"10.2215\/CJN.04100808","article-title":"Serum phosphorus concentrations and arterial stiffness among individuals with normal kidney function to moderate kidney disease in MESA","volume":"4","author":"Ix","year":"2009","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"B81","doi-asserted-by":"publisher","first-page":"e10","DOI":"10.1161\/01.res.87.7.e10","article-title":"Phosphate regulation of vascular smooth muscle cell calcification","volume":"87","author":"Jono","year":"2000","journal-title":"Circulation Res."},{"key":"B82","doi-asserted-by":"publisher","first-page":"2182","DOI":"10.1097\/HJH.0b013e328357c049","article-title":"Submaximal suppression of parathyroid hormone ameliorates calcitriol-induced aortic calcification and remodeling and myocardial fibrosis in uremic rats","volume":"30","author":"Jung","year":"2012","journal-title":"J. Hypertens."},{"key":"B83","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1359\/jbmr.090806","article-title":"Wnt inhibitors Dkk1 and Sost are downstream targets of BMP signaling through the type IA receptor (BMPRIA) in osteoblasts","volume":"25","author":"Kamiya","year":"2010","journal-title":"J. Bone Mineral Res."},{"key":"B84","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1038\/s12276-021-00671-2","article-title":"Single-cell transcriptome analysis reveals cellular heterogeneity in the ascending aortas of normal and high-fat diet-fed mice","volume":"53","author":"Kan","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"B85","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1161\/CIRCRESAHA.116.305012","article-title":"Vascular smooth muscle cell calcification is mediated by regulated exosome secretion","volume":"116","author":"Kapustin","year":"2015","journal-title":"Circulation Res."},{"key":"B86","doi-asserted-by":"publisher","first-page":"e1008938","DOI":"10.1371\/journal.pgen.1008938","article-title":"The facts of the matter: What is a hormone?","volume":"16","author":"Karsenty","year":"2020","journal-title":"PLOS Genet."},{"key":"B87","doi-asserted-by":"publisher","first-page":"2683","DOI":"10.1681\/ASN.2006070783","article-title":"Parathyroid hormone regulates fibroblast growth factor-23 in a mouse model of primary hyperparathyroidism","volume":"18","author":"Kawata","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"B88","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1038\/ki.2008.407","article-title":"Cinacalcet suppresses calcification of the aorta and heart in uremic rats","volume":"74","author":"Kawata","year":"2008","journal-title":"Kidney Int."},{"key":"B89","doi-asserted-by":"publisher","first-page":"eabm5900","DOI":"10.1126\/sciadv.abm5900","article-title":"Identification of kidney injury-released circulating osteopontin as causal agent of respiratory failure","volume":"8","author":"Khamissi","year":"2022","journal-title":"Sci. Adv."},{"key":"B90","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1681\/ASN.2007121312","article-title":"CKD accelerates development of neointimal hyperplasia in arteriovenous fistulas","volume":"20","author":"Kokubo","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"B91","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1007\/978-1-4419-1050-9_5","article-title":"Regulation of osteoblast differentiation by Runx2","volume":"658","author":"Komori","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1016\/j.stem.2016.08.001","article-title":"Adventitial MSC-like cells are progenitors of vascular smooth muscle cells and drive vascular calcification in chronic kidney disease","volume":"19","author":"Kramann","year":"2016","journal-title":"Cell Stem Cell"},{"key":"B93","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/36285","article-title":"Mutation of the mouse klotho gene leads to a syndrome resembling ageing","volume":"390","author":"Kuro-o","year":"1997","journal-title":"Nature"},{"key":"B94","doi-asserted-by":"publisher","first-page":"6120","DOI":"10.1074\/jbc.C500457200","article-title":"Regulation of fibroblast growth factor-23 signaling by Klotho","volume":"281","author":"Kurosu","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B95","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1126\/science.1112766","article-title":"Suppression of aging in mice by the hormone klotho","volume":"309","author":"Kurosu","year":"2005","journal-title":"Science"},{"key":"B96","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1016\/j.jacc.2021.06.049","article-title":"Medial arterial calcification: JACC state-of-the-art review","volume":"78","author":"Lanzer","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"B97","doi-asserted-by":"publisher","first-page":"2685","DOI":"10.3390\/ijms21082685","article-title":"Vascular calcification-new insights into its mechanism","volume":"21","author":"Lee","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B98","doi-asserted-by":"publisher","first-page":"745892","DOI":"10.3389\/fcell.2021.745892","article-title":"Cardiac fibroblast growth factor 23 excess does not induce left ventricular hypertrophy in healthy mice","volume":"9","author":"Leifheit-Nestler","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"B99","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.1359\/jbmr.070804","article-title":"Control of the SOST bone enhancer by PTH using MEF2 transcription factors","volume":"22","author":"Leupin","year":"2007","journal-title":"J. Bone Mineral Res."},{"key":"B100","first-page":"272","article-title":"Comprehensive associations between acidosis and the skeleton in patients with kidney disease","volume":"13","author":"Levy","year":"2023","journal-title":"J. Am. Soc. Nephrol."},{"key":"B101","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1007\/s11255-018-2033-4","article-title":"Relationship between serum sclerostin, vascular sclerostin expression and vascular calcification assessed by different methods in ESRD patients eligible for renal transplantation: A cross-sectional study","volume":"51","author":"Li","year":"2019","journal-title":"Int. Urology Nephrol."},{"key":"B102","doi-asserted-by":"publisher","first-page":"e150051","DOI":"10.1172\/JCI150051","article-title":"SIRT6 protects vascular smooth muscle cells from osteogenic transdifferentiation via Runx2 in chronic kidney disease","volume":"132","author":"Li","year":"2022","journal-title":"J. Clin. Investigation"},{"key":"B103","doi-asserted-by":"publisher","first-page":"19883","DOI":"10.1074\/jbc.M413274200","article-title":"Sclerostin binds to LRP5\/6 and antagonizes canonical Wnt signaling","volume":"280","author":"Li","year":"2005","journal-title":"J. Biol. Chem."},{"key":"B104","doi-asserted-by":"publisher","first-page":"222","DOI":"10.5414\/CN109650","article-title":"Serum bone markers in ROD patients across the spectrum of decreases in GFR: Activin A increases before all other markers","volume":"91","author":"Lima","year":"2019","journal-title":"Clin. Nephrol."},{"key":"B105","doi-asserted-by":"publisher","first-page":"e0152959","DOI":"10.1371\/journal.pone.0152959","article-title":"Endothelial cells can regulate smooth muscle cells in contractile phenotype through the miR-206\/arf6&ncx1\/exosome Axis","volume":"11","author":"Lin","year":"2016","journal-title":"PLOS ONE"},{"key":"B106","doi-asserted-by":"publisher","first-page":"2169","DOI":"10.1681\/ASN.2013111209","article-title":"The kidney is the principal organ mediating klotho effects","volume":"25","author":"Lindberg","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"B107","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1086\/338450","article-title":"A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait","volume":"70","author":"Little","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"B108","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.yjmcc.2017.11.021","article-title":"High phosphate-induced downregulation of PPAR\u03b3 contributes to CKD-associated vascular calcification","volume":"114","author":"Liu","year":"2018","journal-title":"J. Mol. Cell. Cardiol."},{"key":"B109","doi-asserted-by":"publisher","first-page":"2765","DOI":"10.1016\/j.devcel.2021.09.001","article-title":"H3K4 di-methylation governs smooth muscle lineage identity and promotes vascular homeostasis by restraining plasticity","volume":"56","author":"Liu","year":"2021","journal-title":"Dev. Cell"},{"key":"B110","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1681\/ASN.2005111185","article-title":"Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D","volume":"17","author":"Liu","year":"2006","journal-title":"J. Am. Soc. Nephrol."},{"key":"B111","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.bone.2011.11.016","article-title":"TGF-\u03b2 regulates sclerostin expression via the ECR5 enhancer","volume":"50","author":"Loots","year":"2012","journal-title":"Bone"},{"key":"B112","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1097\/01.asn.0000109671.99498.08","article-title":"Successful treatment of an adynamic bone disorder with bone morphogenetic protein-7 in a renal ablation model","volume":"15","author":"Lund","year":"2004","journal-title":"J. Am. Soc. Nephrol."},{"key":"B113","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/386078a0","article-title":"Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein","volume":"386","author":"Luo","year":"1997","journal-title":"Nature"},{"key":"B114","doi-asserted-by":"publisher","first-page":"115121","DOI":"10.1016\/j.bone.2019.115121","article-title":"Denosumab or romosozumab therapy and risk of cardiovascular events in patients with primary osteoporosis: Systematic review and meta-analysis","volume":"130","author":"Lv","year":"2020","journal-title":"Bone"},{"key":"B115","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1002\/jbmr.4203","article-title":"Chronic kidney disease-induced vascular calcification impairs bone metabolism","volume":"36","author":"Mace","year":"2021","journal-title":"J. Bone Min. Res."},{"key":"B116","doi-asserted-by":"publisher","first-page":"e10610","DOI":"10.1002\/jbm4.10610","article-title":"The calcified vasculature in chronic kidney disease secretes factors that inhibit bone mineralization","volume":"6","author":"Mace","year":"2022","journal-title":"JBMR Plus"},{"key":"B117","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.3389\/fphar.2020.01273","article-title":"High phosphate induces and klotho attenuates kidney epithelial senescence and fibrosis","volume":"11","author":"Maique","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B118","doi-asserted-by":"publisher","first-page":"496","DOI":"10.3390\/genes11050496","article-title":"The role of Wnt signalling in chronic kidney disease (CKD)","volume":"11","author":"Malik","year":"2020","journal-title":"Genes"},{"key":"B119","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nrneph.2013.198","article-title":"Evaluating bone quality in patients with chronic kidney disease","volume":"9","author":"Malluche","year":"2013","journal-title":"Nat. Rev. Nephrol."},{"key":"B120","doi-asserted-by":"publisher","first-page":"e1008714","DOI":"10.1371\/journal.pgen.1008714","article-title":"Osteocalcin promotes bone mineralization but is not a hormone","volume":"16","author":"Manolagas","year":"2020","journal-title":"PLOS Genet."},{"key":"B121","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1152\/physrev.00002.2011","article-title":"Regulation and function of the FGF23\/klotho endocrine pathways","volume":"92","author":"Martin","year":"2012","journal-title":"Physiol. Rev."},{"key":"B122","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1016\/j.kint.2019.06.025","article-title":"Chronic kidney disease and valvular heart disease: Conclusions from a kidney disease: Improving global outcomes (KDIGO) controversies conference","volume":"96","author":"Marwick","year":"2019","journal-title":"Kidney Int."},{"key":"B123","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1681\/ASN.2007070760","article-title":"The mechanism of phosphorus as a cardiovascular risk factor in CKD","volume":"19","author":"Mathew","year":"2008","journal-title":"J. Am. Soc. Nephrol."},{"key":"B124","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1681\/ASN.2014020173","article-title":"Subclinical atherosclerosis measures for cardiovascular prediction in CKD","volume":"26","author":"Matsushita","year":"2015","journal-title":"J. Am. Soc. Nephrol. JASN."},{"key":"B125","doi-asserted-by":"publisher","first-page":"2796","DOI":"10.1681\/ASN.2005030291","article-title":"Cardiac and vascular adaptation in pediatric patients with chronic kidney disease: Role of calcium-phosphorus metabolism","volume":"16","author":"Mitsnefes","year":"2005","journal-title":"J. Am. Soc. Nephrol."},{"key":"B126","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.1038\/sj.ki.5000414","article-title":"Definition, evaluation, and classification of renal osteodystrophy: A position statement from kidney disease: Improving global outcomes (kdigo)","volume":"69","author":"Moe","year":"2006","journal-title":"Kidney Int."},{"key":"B127","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.2215\/CJN.09500916","article-title":"Fractures in patients with CKD: Time for action","volume":"11","author":"Moe","year":"2016","journal-title":"Clin. J. Am. Soc. Nephrol. CJASN."},{"key":"B128","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1046\/j.1523-1755.2002.00170.x","article-title":"Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins","volume":"61","author":"Moe","year":"2002","journal-title":"Kidney Int."},{"key":"B129","doi-asserted-by":"publisher","first-page":"784","DOI":"10.2741\/4337","article-title":"Chronic kidney disease alters vascular smooth muscle cell phenotype","volume":"20","author":"Monroy","year":"2015","journal-title":"Front. Biosci. (Landmark Ed."},{"key":"B130","doi-asserted-by":"publisher","first-page":"185","DOI":"10.3390\/toxins12030185","article-title":"Klotho\/FGF23 and Wnt signaling as important players in the comorbidities associated with chronic kidney disease","volume":"12","author":"Mu\u00f1oz-Casta\u00f1eda","year":"2020","journal-title":"Toxins (Basel)"},{"key":"B131","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1093\/cvr\/cvs126","article-title":"Sources of cells that contribute to atherosclerotic intimal calcification: An in vivo genetic fate mapping study","volume":"94","author":"Naik","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"B132","doi-asserted-by":"publisher","first-page":"2512","DOI":"10.1681\/ASN.2014101034","article-title":"Cause-specific deaths in non\u2013dialysis-dependent CKD","volume":"26","author":"Navaneethan","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"B133","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.jacbts.2020.02.002","article-title":"Targeting vascular calcification in chronic kidney disease","volume":"5","author":"Nelson","year":"2020","journal-title":"JACC Basic Transl. Sci."},{"key":"B134","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1038\/sj.ki.5002241","article-title":"Vascular calcification: Contribution of parathyroid hormone in renal failure","volume":"71","author":"Neves","year":"2007","journal-title":"Kidney Int."},{"key":"B135","doi-asserted-by":"publisher","first-page":"e126467","DOI":"10.1172\/jci.insight.126467","article-title":"Vitamin D\u2013regulated osteocytic sclerostin and BMP2 modulate uremic extraskeletal calcification","volume":"4","author":"Nguyen-Yamamoto","year":"2019","journal-title":"JCI Insight"},{"key":"B136","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1002\/jbmr.1916","article-title":"Rapid cortical bone loss in patients with chronic kidney disease","volume":"28","author":"Nickolas","year":"2013","journal-title":"J. Bone Mineral Res."},{"key":"B137","doi-asserted-by":"publisher","first-page":"8520","DOI":"10.1038\/sj.onc.1207892","article-title":"DKK1, a negative regulator of Wnt signaling, is a target of the \u03b2-catenin\/TCF pathway","volume":"23","author":"Niida","year":"2004","journal-title":"Oncogene"},{"key":"B138","doi-asserted-by":"publisher","first-page":"1946","DOI":"10.1001\/jama.2021.4807","article-title":"Effect of treating hyperphosphatemia with lanthanum carbonate vs calcium carbonate on cardiovascular events in patients with chronic kidney disease undergoing hemodialysis: The LANDMARK randomized clinical trial","volume":"325","author":"Ogata","year":"2021","journal-title":"JAMA"},{"key":"B139","volume-title":"KDIGO:Clinical guide to bone and mineral metabolism in CKD","author":"Olgaard","year":"2006"},{"key":"B140","doi-asserted-by":"publisher","first-page":"4751","DOI":"10.3390\/ijms23094751","article-title":"Sclerostin: From molecule to clinical biomarker","volume":"23","author":"Omran","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B141","doi-asserted-by":"publisher","first-page":"1637","DOI":"10.1681\/ASN.2010040349","article-title":"Matrix remodeling in vascular calcification associated with chronic kidney disease","volume":"21","author":"Pai","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"B142","doi-asserted-by":"publisher","first-page":"F891","DOI":"10.1152\/ajprenal.00163.2014","article-title":"A current understanding of vascular calcification in CKD","volume":"307","author":"Paloian","year":"2014","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"B143","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1016\/j.bone.2009.08.008","article-title":"Patterns of FGF-23, DMP1 and MEPE expression in patients with chronic kidney disease","volume":"45","author":"Pereira","year":"2009","journal-title":"Bone"},{"key":"B144","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1681\/ASN.2020101398","article-title":"A randomized trial of tenapanor and phosphate binders as a dual-mechanism treatment for hyperphosphatemia in patients on maintenance dialysis (AMPLIFY)","volume":"32","author":"Pergola","year":"2021","journal-title":"J. Am. Soc. Nephrol."},{"key":"B145","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/j.molmed.2009.07.001","article-title":"Vascular calcification and bone disease: The calcification paradox","volume":"15","author":"Persy","year":"2009","journal-title":"Trends Mol. Med."},{"key":"B146","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1161\/01.res.87.11.1055","article-title":"Apoptosis regulates human vascular calcification in vitro: Evidence for initiation of vascular calcification by apoptotic bodies","volume":"87","author":"Proudfoot","year":"2000","journal-title":"Circulation Res."},{"key":"B147","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1038\/ki.2015.194","article-title":"Increased circulating sclerostin levels in end-stage renal disease predict biopsy-verified vascular medial calcification and coronary artery calcification","volume":"88","author":"Qureshi","year":"2015","journal-title":"Kidney Int."},{"key":"B148","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1161\/CIRCULATIONAHA.119.044195","article-title":"Slowing progression of cardiovascular calcification with SNF472 in patients on hemodialysis: Results of a randomized phase 2b study","volume":"141","author":"Raggi","year":"2020","journal-title":"Circulation"},{"key":"B149","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/s0735-1097(01)01781-8","article-title":"Cardiac calcification in adult hemodialysis patients. A link between end-stage renal disease and cardiovascular disease?","volume":"39","author":"Raggi","year":"2002","journal-title":"J. Am. Coll. Cardiol."},{"key":"B150","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1093\/ndt\/gfq725","article-title":"The ADVANCE study: A randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on hemodialysis","volume":"26","author":"Raggi","year":"2011","journal-title":"Nephrol. Dial. Transpl."},{"key":"B151","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1359\/JBMR.041221","article-title":"Decrease in thoracic vertebral bone attenuation with calcium-based phosphate binders in hemodialysis","volume":"20","author":"Raggi","year":"2005","journal-title":"J. Bone Mineral Res."},{"key":"B152","doi-asserted-by":"publisher","first-page":"F477","DOI":"10.1152\/ajprenal.00472.2015","article-title":"Effect of chronic uremia on the transcriptional profile of the calcified aorta analyzed by RNA sequencing","volume":"310","author":"Rukov","year":"2016","journal-title":"Am. J. Physiology - Ren. Physiology"},{"key":"B153","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1002\/jbmr.1630","article-title":"Repression of osteocyte Wnt\/\u03b2-catenin signaling is an early event in the progression of renal osteodystrophy","volume":"27","author":"Sabbagh","year":"2012","journal-title":"J. Bone Min. Res."},{"key":"B154","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1007\/s00223-022-01031-6","article-title":"One-year romosozumab treatment followed by one-year denosumab treatment for osteoporosis in patients on hemodialysis: An observational study","volume":"112","author":"Saito","year":"2022","journal-title":"Calcif. Tissue Int."},{"key":"B155","doi-asserted-by":"publisher","first-page":"e86301","DOI":"10.1371\/journal.pone.0086301","article-title":"Reduced renal \u03b1-klotho expression in CKD patients and its effect on renal phosphate handling and vitamin D metabolism","volume":"9","author":"Sakan","year":"2014","journal-title":"PLoS ONE"},{"key":"B156","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.1161\/ATVBAHA.110.204859","article-title":"Serum osteocalcin is associated with measures of insulin resistance, adipokine levels, and the presence of metabolic syndrome","volume":"30","author":"Saleem","year":"2010","journal-title":"Arteriosclerosis, Thrombosis, Vasc. Biol."},{"key":"B157","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1007\/s00774-021-01253-y","article-title":"Efficacy of romosozumab in patients with osteoporosis on maintenance hemodialysis in Japan; an observational study","volume":"39","author":"Sato","year":"2021","journal-title":"J. Bone Min. Metab."},{"key":"B158","doi-asserted-by":"publisher","first-page":"36","DOI":"10.3389\/fcvm.2018.00036","article-title":"Initiation and propagation of vascular calcification is regulated by a concert of platelet- and smooth muscle cell-derived extracellular vesicles","volume":"5","author":"Schurgers","year":"2018","journal-title":"Front. Cardiovasc. Med."},{"key":"B159","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.bone.2016.10.009","article-title":"Transcriptional control of Sost in bone","volume":"96","author":"Sebastian","year":"2017","journal-title":"Bone"},{"key":"B160","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1159\/000353569","article-title":"Effects of phosphate binder therapy on vascular stiffness in early-stage chronic kidney disease","volume":"38","author":"Seifert","year":"2013","journal-title":"Amer J. Nephrol."},{"key":"B161","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1159\/000362251","article-title":"Left ventricular mass progression despite stable blood pressure and kidney function in stage 3 chronic kidney disease","volume":"39","author":"Seifert","year":"2014","journal-title":"Am. J. Nephrol."},{"key":"B162","doi-asserted-by":"publisher","first-page":"2393","DOI":"10.1172\/JCI117246","article-title":"High expression of genes for calcification-regulating proteins in human atherosclerotic plaques","volume":"93","author":"Shanahan","year":"1994","journal-title":"J. Clin. Invest."},{"key":"B163","doi-asserted-by":"publisher","first-page":"2168","DOI":"10.1161\/01.cir.100.21.2168","article-title":"Medial localization of mineralization-regulating proteins in association with Monckeberg's sclerosis: Evidence for smooth muscle cell-mediated vascular calcification","volume":"100","author":"Shanahan","year":"1999","journal-title":"Circulation"},{"key":"B164","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1161\/CIRCRESAHA.110.234914","article-title":"Arterial calcification in chronic kidney disease: Key roles for calcium and phosphate","volume":"109","author":"Shanahan","year":"2011","journal-title":"Circ. Res."},{"key":"B165","doi-asserted-by":"publisher","first-page":"40589","DOI":"10.1074\/jbc.M504166200","article-title":"The vitamin D receptor, Runx2, and the notch signaling pathway cooperate in the transcriptional regulation of osteopontin","volume":"280","author":"Shen","year":"2005","journal-title":"J. Biol. Chem."},{"key":"B166","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1093\/ndt\/gfg513","article-title":"Lower risk for cardiovascular mortality in oral 1alpha-hydroxy vitamin D3 users in a haemodialysis population","volume":"19","author":"Shoji","year":"2004","journal-title":"Nephrol. Dial. Transpl."},{"key":"B167","doi-asserted-by":"publisher","first-page":"3263","DOI":"10.1093\/ndt\/gfn226","article-title":"The circulating calcification inhibitors, fetuin-A and osteoprotegerin, but not Matrix Gla protein, are associated with vascular stiffness and calcification in children on dialysis","volume":"23","author":"Shroff","year":"2008","journal-title":"Nephrol. Dial. Transplant."},{"key":"B168","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1084\/jem.20020911","article-title":"Inactivation of the osteopontin gene enhances vascular calcification of matrix Gla protein-deficient mice: Evidence for osteopontin as an inducible inhibitor of vascular calcification in vivo","volume":"196","author":"Speer","year":"2002","journal-title":"J. Exp. Med."},{"key":"B169","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1161\/CIRCRESAHA.108.183053","article-title":"Smooth muscle cells give rise to osteochondrogenic precursors and chondrocytes in calcifying arteries","volume":"104","author":"Speer","year":"2009","journal-title":"Circ. Res."},{"key":"B170","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.1002\/jcp.25282","article-title":"E11\/Podoplanin protein stabilization through inhibition of the proteasome promotes osteocyte differentiation in murine in vitro models","volume":"231","author":"Staines","year":"2016","journal-title":"J. Cell Physiol."},{"key":"B171","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1161\/hh2401.101070","article-title":"Smooth muscle cell phenotypic transition associated with calcification: Upregulation of Cbfa1 and downregulation of smooth muscle lineage markers","volume":"89","author":"Steitz","year":"2001","journal-title":"Circulation Res."},{"key":"B172","doi-asserted-by":"publisher","first-page":"2035","DOI":"10.1016\/S0002-9440(10)64482-3","article-title":"Osteopontin inhibits mineral deposition and promotes regression of ectopic calcification","volume":"161","author":"Steitz","year":"2002","journal-title":"Am. J. Pathol."},{"key":"B173","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.kint.2016.07.039","article-title":"Ligand trap of the activin receptor type IIA inhibits osteoclast stimulation of bone remodeling in diabetic mice with chronic kidney disease","volume":"91","author":"Sugatani","year":"2017","journal-title":"Kidney Int."},{"key":"B174","doi-asserted-by":"publisher","first-page":"F431","DOI":"10.1152\/ajprenal.0009.2001","article-title":"A role for Wnt-4 in renal fibrosis","volume":"282","author":"Surendran","year":"2002","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"B175","doi-asserted-by":"publisher","first-page":"2373","DOI":"10.1681\/ASN.2004110949","article-title":"Wnt-dependent- \u03b2-catenin signaling is activated after unilateral ureteral obstruction, and recombinant secreted frizzled-related protein 4 alters the progression of renal fibrosis","volume":"16","author":"Surendran","year":"2005","journal-title":"J. Am. Soc. Nephrol."},{"key":"B176","first-page":"245A","article-title":"A putative Wnt antagonist secreted frizzled-related protein 4 (sFRP4) suppresses the progression of renal fibrosis follwoing unilateral ureteral obstruction","volume":"15","author":"Surendran","year":"2004","journal-title":"J. Am. Soc. Nephrol."},{"key":"B177","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.7326\/M21-3324","article-title":"Vitamin D deficiency increases mortality risk in the UK biobank: A nonlinear mendelian randomization study","volume":"175","author":"Sutherland","year":"2022","journal-title":"Ann. Intern. Med."},{"key":"B178","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1038\/s41581-020-0309-2","article-title":"Autophagy in kidney homeostasis and disease","volume":"16","author":"Tang","year":"2020","journal-title":"Nat. Rev. Nephrol."},{"key":"B179","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1001\/jama.2012.120","article-title":"Vitamin d therapy and cardiac structure and function in patients with chronic kidney disease: The PRIMO randomized controlled trial","volume":"307","author":"Thadhani","year":"2012","journal-title":"JAMA"},{"key":"B180","doi-asserted-by":"publisher","first-page":"2034","DOI":"10.1681\/ASN.2005101085","article-title":"Chronic kidney disease and mortality risk: A systematic review","volume":"17","author":"Tonelli","year":"2006","journal-title":"J. Am. Soc. Nephrol."},{"key":"B181","doi-asserted-by":"publisher","first-page":"2653","DOI":"10.1681\/ASN.2020040411","article-title":"A randomized trial on the effect of phosphate reduction on vascular end points in CKD (IMPROVE-CKD)","volume":"31","author":"Toussaint","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"B182","doi-asserted-by":"publisher","first-page":"30427","DOI":"10.1074\/jbc.273.46.30427","article-title":"Diet-induced diabetes activates an osteogenic gene regulatory program in the aortas of low density lipoprotein receptor-deficient mice","volume":"273","author":"Towler","year":"1998","journal-title":"J. Biol. Chem."},{"key":"B183","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1038\/nature05315","article-title":"Klotho converts canonical FGF receptor into a specific receptor for FGF23","volume":"444","author":"Urakawa","year":"2006","journal-title":"Nature"},{"key":"B184","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1161\/ATVBAHA.106.132266","article-title":"Characterization of phosphate transport in rat vascular smooth muscle cells: Implications for vascular calcification","volume":"27","author":"Villa-Bellosta","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"B185","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1055\/s-0037-1614168","article-title":"Modulation of the binding of matrix Gla protein (MGP) to bone morphogenetic protein-2 (BMP-2)","volume":"84","author":"Wallin","year":"2000","journal-title":"Thromb. Haemost."},{"key":"B186","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1002\/jbmr.2381","article-title":"HDAC5 controls MEF2C-driven sclerostin expression in osteocytes","volume":"30","author":"Wein","year":"2015","journal-title":"J. Bone Mineral Res."},{"key":"B187","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1053\/j.ajkd.2011.10.041","article-title":"Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: A randomized trial","volume":"59","author":"Westenfeld","year":"2012","journal-title":"Am. J. Kidney Dis."},{"key":"B188","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.jsbmb.2015.12.006","article-title":"Early response of the human SOST gene to stimulation by 1\u03b1,25-dihydroxyvitamin D3","volume":"164","author":"Wijenayaka","year":"2016","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"B189","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.kint.2017.06.016","article-title":"The activin receptor is stimulated in the skeleton, vasculature, heart, and kidney during chronic kidney disease","volume":"93","author":"Williams","year":"2018","journal-title":"Kidney Int."},{"key":"B190","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1038\/ki.2012.176","article-title":"Update on fibroblast growth factor 23 in chronic kidney disease","volume":"82","author":"Wolf","year":"2012","journal-title":"Kidney Int."},{"key":"B191","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1097\/01.mnh.0000447020.74593.6f","article-title":"Coupling fibroblast growth factor 23 production and cleavage: Iron deficiency, rickets, and kidney disease","volume":"23","author":"Wolf","year":"2014","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"B192","doi-asserted-by":"publisher","first-page":"624037","DOI":"10.1155\/2015\/624037","article-title":"Runx2\/miR-3960\/miR-2861 positive feedback loop is responsible for osteogenic transdifferentiation of vascular smooth muscle cells","volume":"2015","author":"Xia","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"B193","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1038\/ncomms2240","article-title":"Cardioprotection by Klotho through downregulation of TRPC6 channels in the mouse heart","volume":"3","author":"Xie","year":"2012","journal-title":"Nat. Commun."},{"key":"B194","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1681\/ASN.2014040325","article-title":"Soluble klotho protects against uremic cardiomyopathy independently of fibroblast growth factor 23 and phosphate","volume":"26","author":"Xie","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"B195","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1681\/ASN.2021101327","article-title":"Interventions to attenuate vascular calcification progression in chronic kidney disease: A systematic review of clinical trials","volume":"33","author":"Xu","year":"2022","journal-title":"J. Am. Soc. Nephrol."},{"key":"B196","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1016\/j.bbrc.2004.02.075","article-title":"USAG-1: A bone morphogenetic protein antagonist abundantly expressed in the kidney","volume":"316","author":"Yanagita","year":"2004","journal-title":"Biochem. Biophysical Res. Commun."},{"key":"B197","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1172\/JCI25445","article-title":"Uterine sensitization-associated gene-1 (USAG-1), a novel BMP antagonist expressed in the kidney, accelerates tubular injury","volume":"116","author":"Yanagita","year":"2006","journal-title":"J. Clin. Invest."},{"key":"B198","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.kint.2022.03.028","article-title":"Soluble alpha-klotho and heparin modulate the pathologic cardiac actions of fibroblast growth factor 23 in chronic kidney disease","volume":"102","author":"Yanucil","year":"2022","journal-title":"Kidney Int."},{"key":"B199","doi-asserted-by":"publisher","first-page":"4241","DOI":"10.1038\/s41467-022-31997-8","article-title":"Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation","volume":"13","author":"Yu","year":"2022","journal-title":"Nat. Commun."},{"key":"B200","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1038\/s41467-022-28096-z","article-title":"A Klotho-derived peptide protects against kidney fibrosis by targeting TGF-\u03b2 signaling","volume":"13","author":"Yuan","year":"2022","journal-title":"Nat. Commun."},{"key":"B201","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1681\/asn.2022010080","article-title":"Coronary artery calcification score and the progression of chronic kidney disease","volume":"33","author":"Yun","year":"2022","journal-title":"J. Am. Soc. Nephrol."},{"key":"B202","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/labinvest.2015.153","article-title":"Wnt\/\u03b2-catenin signaling in kidney injury and repair: A double-edged sword","volume":"96","author":"Zhou","year":"2016","journal-title":"Lab. Investig."},{"key":"B203","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1007\/s11255-017-1604-0","article-title":"Radial artery sclerostin expression in chronic kidney disease stage 5 predialysis patients: A cross-sectional observational study","volume":"49","author":"Zhou","year":"2017","journal-title":"Int. Urology Nephrol."},{"key":"B204","doi-asserted-by":"publisher","first-page":"3211","DOI":"10.1016\/j.ajpath.2015.08.004","article-title":"Klotho ameliorates kidney injury and fibrosis and normalizes blood pressure by targeting the renin-angiotensin system","volume":"185","author":"Zhou","year":"2015","journal-title":"Am. J. Pathology"},{"key":"B205","doi-asserted-by":"publisher","first-page":"e19595","DOI":"10.1371\/journal.pone.0019595","article-title":"The appearance and modulation of osteocyte marker expression during calcification of vascular smooth muscle cells","volume":"6","author":"Zhu","year":"2011","journal-title":"PLoS One"},{"key":"B206","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1097\/MOL.0b013e328011c6fc","article-title":"Vitamin D and vascular calcification","volume":"18","author":"Zittermann","year":"2007","journal-title":"Curr. Opin. Lipidol."},{"key":"B207","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1111\/nep.13472","article-title":"New insights into the role and mechanism of Wnt\/\u03b2-catenin signalling in kidney fibrosis","volume":"23","author":"Zuo","year":"2018","journal-title":"Nephrology"}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2023.1120308\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T01:22:56Z","timestamp":1674696176000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2023.1120308\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,26]]},"references-count":207,"alternative-id":["10.3389\/fphys.2023.1120308"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2023.1120308","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,26]]},"article-number":"1120308"}}