{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T20:21:23Z","timestamp":1793218883610,"version":"4.5.0"},"reference-count":69,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR071614"],"award-info":[{"award-number":["AR071614"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012443","name":"Maryland Stem Cell Research Fund","doi-asserted-by":"publisher","award":["2018-MSCRFD-4246"],"award-info":[{"award-number":["2018-MSCRFD-4246"]}],"id":[{"id":"10.13039\/100012443","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["19POST34450156"],"award-info":[{"award-number":["19POST34450156"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR071618 HL142290"],"award-info":[{"award-number":["AR071618 HL142290"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM008181"],"award-info":[{"award-number":["GM008181"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR007592"],"award-info":[{"award-number":["AR007592"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    The downregulation of sclerostin in osteocytes mediates bone formation in response to mechanical cues and parathyroid hormone (PTH). To date, the regulation of sclerostin has been attributed exclusively to the transcriptional downregulation of the\n                    <jats:italic>Sost<\/jats:italic>\n                    gene hours after stimulation. Using mouse models and rodent cell lines, we describe the rapid, minute-scale post-translational degradation of sclerostin protein by the lysosome following mechanical load and PTH. We present a model, integrating both new and established mechanically and hormonally activated effectors into the regulated degradation of sclerostin by lysosomes. Using a mouse forelimb mechanical loading model, we find transient inhibition of lysosomal degradation or the upstream mechano-signaling pathway controlling sclerostin abundance impairs subsequent load-induced bone formation by preventing sclerostin degradation. We also link dysfunctional lysosomes to aberrant sclerostin regulation using human Gaucher disease iPSCs. These results reveal how bone anabolic cues post-translationally regulate sclerostin abundance in osteocytes to regulate bone formation.\n                  <\/jats:p>","DOI":"10.7554\/elife.64393","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T08:00:36Z","timestamp":1617004836000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.64393","source":"Crossref","is-referenced-by-count":39,"title":["Disparate bone anabolic cues activate bone formation by regulating the rapid lysosomal degradation of sclerostin protein"],"prefix":"10.7554","volume":"10","author":[{"given":"Nicole R","family":"Gould","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3729-0630","authenticated-orcid":true,"given":"Katrina M","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humberto C","family":"Joca","sequence":"additional","affiliation":[{"name":"Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3405-6259","authenticated-orcid":true,"given":"Olivia M","family":"Torre","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S","family":"Lyons","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna M","family":"Leser","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manasa P","family":"Srikanth","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramzi J","family":"Khairallah","sequence":"additional","affiliation":[{"name":"Myologica, LLC, New Market, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo A","family":"Feldman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher W","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1610-4694","authenticated-orcid":true,"given":"Joseph P","family":"Stains","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2021,3,29]]},"reference":[{"key":"bib1","volume-title":"SOST-Related Sclerosing Bone Dysplasias","author":"Appelman-Dijkstra","year":"1993"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1016\/j.bbrc.2013.01.052","article-title":"Simultaneous tracking of 3D actin and microtubule strains in individual MLO-Y4 osteocytes under oscillatory flow","volume":"431","author":"Baik","year":"2013","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1093\/hmg\/10.5.537","article-title":"Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST)","volume":"10","author":"Balemans","year":"2001","journal-title":"Human Molecular Genetics"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1136\/jmg.39.2.91","article-title":"Identification of a 52 kb deletion downstream of the SOST gene in patients with van buchem disease","volume":"39","author":"Balemans","year":"2002","journal-title":"Journal of Medical Genetics"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1080\/14712598.2017.1280455","article-title":"Romosozumab for the treatment of osteoporosis","volume":"17","author":"Bandeira","year":"2017","journal-title":"Expert Opinion on Biological Therapy"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.coph.2018.04.011","article-title":"Targeting WNT signaling in the treatment of osteoporosis","volume":"40","author":"Baron","year":"2018","journal-title":"Current Opinion in Pharmacology"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"4577","DOI":"10.1210\/en.2005-0239","article-title":"Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis","volume":"146","author":"Bellido","year":"2005","journal-title":"Endocrinology"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1111\/j.1365-2818.2006.01706.x","article-title":"A guided tour into subcellular colocalization analysis in light microscopy","volume":"224","author":"Bolte","year":"2006","journal-title":"Journal of Microscopy"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"35939","DOI":"10.1074\/jbc.M109.060335","article-title":"The matricellular protein periostin is required for sost inhibition and the anabolic response to mechanical loading and physical activity","volume":"284","author":"Bonnet","year":"2009","journal-title":"Journal of Biological Chemistry"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"15048","DOI":"10.1073\/pnas.1203085109","article-title":"Regulation of beta catenin signaling and parathyroid hormone anabolic effects in bone by the matricellular protein periostin","volume":"109","author":"Bonnet","year":"2012","journal-title":"PNAS"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.bbamcr.2008.10.016","article-title":"Sorting of lysosomal proteins","volume":"1793","author":"Braulke","year":"2009","journal-title":"Biochimica Et Biophysica Acta (BBA) - Molecular Cell Research"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1086\/318811","article-title":"Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein","volume":"68","author":"Brunkow","year":"2001","journal-title":"The American Journal of Human Genetics"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.1002\/jbmr.3152","article-title":"Connexin43 and Runx2 interact to affect cortical bone geometry, skeletal development, and osteoblast and osteoclast function","volume":"32","author":"Buo","year":"2017","journal-title":"Journal of Bone and Mineral Research"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1359\/jbmr.091001","article-title":"Androgen receptor disruption increases the osteogenic response to mechanical loading in male mice","volume":"25","author":"Callewaert","year":"2010","journal-title":"Journal of Bone and Mineral Research"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1007\/s00418-014-1194-1","article-title":"Decreased activity of osteocyte autophagy with aging may contribute to the bone loss in senile population","volume":"142","author":"Chen","year":"2014","journal-title":"Histochemistry and Cell Biology"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1016\/j.bone.2006.09.008","article-title":"Skeletal actions of intermittent parathyroid hormone: effects on bone remodelling and structure","volume":"40","author":"Compston","year":"2007","journal-title":"Bone"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1002\/jbmr.1805","article-title":"Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR histomorphometry nomenclature committee","volume":"28","author":"Dempster","year":"2013","journal-title":"Journal of Bone and Mineral Research"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.bone.2016.12.004","article-title":"Hormonal and systemic regulation of sclerostin","volume":"96","author":"Drake","year":"2017","journal-title":"Bone"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1111\/tra.12083","article-title":"Rab27 effectors, pleiotropic regulators in secretory pathways","volume":"14","author":"Fukuda","year":"2013","journal-title":"Traffic"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1007\/s11914-019-00520-2","article-title":"Integrins in Osteocyte biology and mechanotransduction","volume":"17","author":"Geoghegan","year":"2019","journal-title":"Current Osteoporosis Reports"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1002\/cbf.3164","article-title":"The anabolic action of intermittent parathyroid hormone on cortical bone depends partly on its ability to induce nitric oxide-mediated vasorelaxation in BALB\/c mice","volume":"34","author":"Gohin","year":"2016","journal-title":"Cell Biochemistry and Function"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1016\/j.cellsig.2016.04.014","article-title":"Communication of cAMP by connexin43 gap junctions regulates osteoblast signaling and gene expression","volume":"28","author":"Gupta","year":"2016","journal-title":"Cellular Signalling"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1515\/iss-2016-0021","article-title":"Mechanobiology of bone remodeling and fracture healing in the aged organism","volume":"1","author":"Haffner-Luntzer","year":"2016","journal-title":"Innovative Surgical Sciences"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1007\/s11914-017-0402-z","article-title":"Aging, Osteocytes, and mechanotransduction","volume":"15","author":"Hemmatian","year":"2017","journal-title":"Current Osteoporosis Reports"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1002\/jbmr.3734","article-title":"Gaucher disease in bone: from pathophysiology to practice","volume":"34","author":"Hughes","year":"2019","journal-title":"Journal of Bone and Mineral Research"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1002\/jbmr.268","article-title":"Rab27a and Rab27b are involved in stimulation-dependent RANKL release from secretory lysosomes in osteoblastic cells","volume":"26","author":"Kariya","year":"2011","journal-title":"Journal of Bone and Mineral Research"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/978-1-62703-989-5_11","article-title":"Preparation of thin frozen sections from nonfixed and undecalcified hard tissues using Kawamot's film method (2012)","volume":"1130","author":"Kawamoto","year":"2014","journal-title":"Methods in Molecular Biology"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.bone.2005.03.018","article-title":"SOST is a target gene for PTH in bone","volume":"37","author":"Keller","year":"2005","journal-title":"Bone"},{"key":"bib29","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9526","article-title":"Detyrosinated microtubules modulate mechanotransduction in heart and skeletal muscle","volume":"6","author":"Kerr","year":"2015","journal-title":"Nature Communications"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1006\/bbrc.1998.9270","article-title":"Nitric oxide response to shear stress by human bone cell cultures is endothelial nitric oxide synthase dependent","volume":"250","author":"Klein-Nulend","year":"1998","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1007\/s00198-013-2590-4","article-title":"Nitric oxide signaling in mechanical adaptation of bone","volume":"25","author":"Klein-Nulend","year":"2014","journal-title":"Osteoporosis International : A Journal Established as Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/S8756-3282(02)00842-6","article-title":"Validation of a technique for studying functional adaptation of the mouse ulna in response to mechanical loading","volume":"31","author":"Lee","year":"2002","journal-title":"Bone"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"S92","DOI":"10.1016\/j.molmet.2019.06.014","article-title":"beta-cell autophagy: mechanism and role in beta-cell dysfunction","volume":"27S","author":"Lee","year":"2019","journal-title":"Molecular Metabolism"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1359\/jbmr.080216","article-title":"Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength","volume":"23","author":"Li","year":"2008","journal-title":"Journal of Bone and Mineral Research"},{"key":"bib35","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01272-2","article-title":"CaMKII-mediated beclin 1 phosphorylation regulates autophagy that promotes degradation of id and neuroblastoma cell differentiation","volume":"8","author":"Li","year":"2017","journal-title":"Nature Communications"},{"key":"bib36","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101098","article-title":"Targeting autophagy in osteoporosis: from pathophysiology to potential therapy","volume":"62","author":"Li","year":"2020","journal-title":"Ageing Research Reviews"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"4173","DOI":"10.1016\/j.jbiomech.2016.11.051","article-title":"Novel multi-functional fluid flow device for studying cellular mechanotransduction","volume":"49","author":"Lyons","year":"2016","journal-title":"Journal of Biomechanics"},{"key":"bib38","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aan5748","article-title":"Microtubules tune mechanotransduction through NOX2 and TRPV4 to decrease sclerostin abundance in osteocytes","volume":"10","author":"Lyons","year":"2017","journal-title":"Science Signaling"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1177\/1759720X17726744","article-title":"Sclerostin antibodies in osteoporosis: latest evidence and therapeutic potential","volume":"9","author":"McClung","year":"2017","journal-title":"Therapeutic Advances in Musculoskeletal Disease"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1002\/jbmr.2222","article-title":"Age-related impairment of bones' adaptive response to loading in mice is associated with sex-related deficiencies in osteoblasts but no change in osteocytes","volume":"29","author":"Meakin","year":"2014","journal-title":"Journal of Bone and Mineral Research"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/978-1-4939-1619-1_9","article-title":"In vivo axial loading of the mouse tibia","volume":"1226","author":"Melville","year":"2015","journal-title":"Methods in Molecular Biology"},{"key":"bib42","doi-asserted-by":"publisher","DOI":"10.1177\/1559325820934227","article-title":"Lysosomes, Autophagy, and hormesis in cell physiology, pathology, and Age-Related disease","volume":"18","author":"Moore","year":"2020","journal-title":"Dose-Response"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1242\/jcs.197285","article-title":"Defective signaling, osteoblastogenesis and bone remodeling in a mouse model of connexin 43 C-terminal truncation","volume":"130","author":"Moorer","year":"2017","journal-title":"Journal of Cell Science"},{"key":"bib44","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-018-0007-x","article-title":"Mechanically induced Ca2+ oscillations in osteocytes release extracellular vesicles and enhance bone formation","volume":"6","author":"Morrell","year":"2018","journal-title":"Bone Research"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s11626-018-0304-0","article-title":"Production of 8-nitro-cGMP in Osteocytic cells and its upregulation by parathyroid hormone and prostaglandin E2","volume":"55","author":"Nagayama","year":"2019","journal-title":"In Vitro Cellular & Developmental Biology - Animal"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1093\/hmg\/ddx442","article-title":"Gaucher disease iPSC-derived osteoblasts have developmental and lysosomal defects that impair bone matrix deposition","volume":"27","author":"Panicker","year":"2018","journal-title":"Human Molecular Genetics"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1677\/jme.0.0250073","article-title":"Parathyroid hormone induces rat interstitial collagenase mRNA through Ets-1 facilitated by cyclic AMP response element-binding protein and Ca(2+)\/calmodulin-dependent protein kinase II in osteoblastic cells","volume":"25","author":"Quinn","year":"2000","journal-title":"Journal of Molecular Endocrinology"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1161\/ATVBAHA.117.309560","article-title":"iNOS-Derived nitric oxide induces Integrin-Linked kinase endocytic Lysosome-Mediated degradation in the vascular endothelium","volume":"37","author":"Reventun","year":"2017","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1042\/BC20050085","article-title":"Intracellular degradation of insulin and crinophagy are maintained by nitric oxide and cyclo-oxygenase 2 activity in isolated pancreatic islets","volume":"98","author":"Sandberg","year":"2006","journal-title":"Biology of the Cell"},{"key":"bib50","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17099-3","article-title":"A FAK\/HDAC5 signaling Axis controls osteocyte mechanotransduction","volume":"11","author":"Sato","year":"2020","journal-title":"Nature Communications"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s00223-013-9790-y","article-title":"Osteocytes: master orchestrators of bone","volume":"94","author":"Schaffler","year":"2014","journal-title":"Calcified Tissue International"},{"key":"bib52","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":"bib53","doi-asserted-by":"publisher","first-page":"16744","DOI":"10.1074\/jbc.M114.628313","article-title":"The wnt inhibitor sclerostin is Up-regulated by mechanical unloading in osteocytes in vitro","volume":"290","author":"Spatz","year":"2015","journal-title":"Journal of Biological Chemistry"},{"key":"bib54","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2019.00308","article-title":"Agephagy - Adapting autophagy for health during aging","volume":"7","author":"Stead","year":"2019","journal-title":"Frontiers in Cell and Developmental Biology"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.gene.2012.04.076","article-title":"Mechanical regulation of signaling pathways in bone","volume":"503","author":"Thompson","year":"2012","journal-title":"Gene"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1091\/mbc.e03-07-0452","article-title":"A general role for Rab27a in secretory cells","volume":"15","author":"Tolmachova","year":"2004","journal-title":"Molecular Biology of the Cell"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"E3632","DOI":"10.1073\/pnas.1701054114","article-title":"NGF-TrkA signaling in sensory nerves is required for skeletal adaptation to mechanical loads in mice","volume":"114","author":"Tomlinson","year":"2017","journal-title":"PNAS"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.bone.2011.10.025","article-title":"Sost downregulation and local wnt signaling are required for the osteogenic response to mechanical loading","volume":"50","author":"Tu","year":"2012","journal-title":"Bone"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"354","DOI":"10.2174\/1389450119666180626120852","article-title":"Autophagy: a promising target for Age-related osteoporosis","volume":"20","author":"Wang","year":"2019","journal-title":"Current Drug Targets"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"4103","DOI":"10.1091\/mbc.e03-01-0022","article-title":"Involvement of the Rab27 binding protein Slac2c\/MyRIP in insulin exocytosis","volume":"14","author":"Waselle","year":"2003","journal-title":"Molecular Biology of the Cell"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"R151","DOI":"10.1530\/JME-13-0241","article-title":"Autophagy in the endocrine glands","volume":"52","author":"Weckman","year":"2014","journal-title":"Journal of Molecular Endocrinology"},{"key":"bib62","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":"Journal of Bone and Mineral Research"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1002\/jbm4.10021","article-title":"Parathyroid hormone signaling in osteocytes","volume":"2","author":"Wein","year":"2018","journal-title":"JBMR Plus"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.ymeth.2015.06.022","article-title":"Exploring G protein-coupled receptor signaling networks using SILAC-based phosphoproteomics","volume":"92","author":"Williams","year":"2016","journal-title":"Methods"},{"key":"bib65","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2020.115356","article-title":"TRPV4 calcium influx controls sclerostin protein loss independent of purinergic calcium oscillations","volume":"136","author":"Williams","year":"2020","journal-title":"Bone"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.bone.2014.06.006","article-title":"Osteocyte-derived RANKL is a critical mediator of the increased bone resorption caused by dietary calcium deficiency","volume":"66","author":"Xiong","year":"2014","journal-title":"Bone"},{"key":"bib67","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0138189","article-title":"Osteocytes, not osteoblasts or lining cells, are the main source of the RANKL required for osteoclast formation in remodeling bone","volume":"10","author":"Xiong","year":"2015","journal-title":"PLOS ONE"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1359\/jbmr.1999.14.7.1123","article-title":"Mechanical strain stimulates nitric oxide production by rapid activation of endothelial nitric oxide synthase in osteocytes","volume":"14","author":"Zaman","year":"1999","journal-title":"Journal of Bone and Mineral Research"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1007\/s12035-018-1142-5","article-title":"Ca2+\/Calmodulin-Dependent protein kinase II (CaMKII) \u03b2-Dependent phosphorylation of GABA1 Triggers Lysosomal Degradation of GABAb>Bb> Receptors via Mind Bomb-2 (MIB2)-Mediated Lys-63-Linked Ubiquitination","volume":"56","author":"Zemoura","year":"2019","journal-title":"Molecular Neurobiology"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/64393\/elife-64393-v3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/64393\/elife-64393-v3.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/64393","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:06:21Z","timestamp":1697058381000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/64393"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,29]]},"references-count":69,"alternative-id":["10.7554\/eLife.64393"],"URL":"https:\/\/doi.org\/10.7554\/elife.64393","archive":["CLOCKSS"],"relation":{"has-review":[{"id-type":"doi","id":"10.7554\/eLife.64393.sa1","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.64393.sa2","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.10.26.355800","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,29]]},"article-number":"e64393"}}