{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T19:00:13Z","timestamp":1791054013755,"version":"4.1.0"},"reference-count":135,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"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. Endocrinol."],"abstract":"<jats:p>Osteoporosis (OP) and its related fragility fractures represent a significant global health burden, primarily characterized by reduced bone mass, deteriorated microarchitecture, and compromised self-repair capacity. While current mainstream therapies focusing on anti-resorption and anabolic pathways can slow bone loss, they often fall short in reversing established skeletal deficits and, particularly, in facilitating fracture healing. Growing evidence underscores that angiogenesis is fundamentally coupled with osteogenesis, forming the cornerstone of bone homeostasis and injury repair. However, developing therapeutic strategies targeting this \u201cvascular-bone\u201d axis remains a relatively nascent and underexplored area in the clinical management of both systemic osteoporosis and osteoporotic fractures. This review aims to provide a comprehensive synthesis of dual strategies targeting angiogenesis for the treatment of systemic osteoporosis and the enhancement of osteoporotic fracture healing. We first analyze the pivotal role and regulatory networks of angiogenesis in maintaining bone homeostasis and within the fracture repair microenvironment. Subsequently, we systematically categorize and critically evaluate various intervention strategies based on this approach, including mesenchymal stem cells and their exosomes with paracrine functions, phytochemicals and traditional Chinese medicine compounds possessing dual regulatory activities, non-coding RNAs (miRNAs, lncRNAs, circRNAs) that modulate key signaling pathways, proteins or peptides with defined pro-angiogenic activity, repurposed clinical drugs with potential vascular-modulating properties, and non-invasive physical therapies. The article further compares and contrasts the application of these strategies for systemic bone mass restoration versus localized fracture repair, discussing differences in delivery methods, molecular targets, and expected outcomes. Finally, we address the current challenges in the field\u2014such as target specificity, translational barriers, and the lack of robust clinical evidence\u2014and outline future research directions. By integrating existing knowledge, this review seeks to provide a theoretical foundation and novel perspectives for developing next-generation, synergistic therapies centered on vascular regeneration, designed to concurrently improve bone mineral density and bone quality.<\/jats:p>","DOI":"10.3389\/fendo.2026.1790054","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T04:26:16Z","timestamp":1775535976000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Unlocking bone repair in osteoporosis by targeting the angiogenic niche"],"prefix":"10.3389","volume":"17","author":[{"given":"Min","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Upper Limbs, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Upper Limbs, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Upper Limbs, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huirong","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Upper Limbs, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.7326\/AITC201708010","article-title":"Osteoporosis","volume":"167","author":"Ensrud","year":"2017","journal-title":"Ann Intern Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-7568(21)00172-0","article-title":"Global, regional, and national burden of bone fractures in 204 countries and territories, 1990-2019: a systematic analysis from the Global Burden of Disease Study 2019","volume":"2","year":"2021","journal-title":"Lancet Healthy Longev"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.882241","article-title":"The global burden of osteoporosis, low bone mass, and its related fracture in 204 countries and territories, 1990-2019","volume":"13","author":"Shen","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B4","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/j.ecl.2012.04.006","article-title":"Pathophysiology of osteoporosis: new mechanistic insights","volume":"41","author":"Armas","year":"2012","journal-title":"Endocrinol Metab Clin North Am"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/nu16142205","article-title":"Impact of combined prebiotic galacto-oligosaccharides and bifidobacterium breve-derived postbiotic on gut microbiota and hbA1c in prediabetic adults: A double-blind, randomized, placebo-controlled study","volume":"16","author":"Beteri","year":"2024","journal-title":"Nutrients"},{"key":"B6","doi-asserted-by":"publisher","first-page":"818","DOI":"10.7326\/M15-1361","article-title":"Treatment of low bone density or osteoporosis to prevent fractures in men and women: a clinical practice guideline update from the American College of Physicians","volume":"166","author":"Qaseem","year":"2017","journal-title":"Ann Intern Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"37","DOI":"10.7326\/M19-0533","article-title":"Long-term drug therapy and drug discontinuations and holidays for osteoporosis fracture prevention: a systematic review","volume":"171","author":"Fink","year":"2019","journal-title":"Ann Intern Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3390\/cells11223552","article-title":"HIF-1\u03b1 regulates bone homeostasis and angiogenesis, participating in the occurrence of bone metabolic diseases","volume":"11","author":"Chen","year":"2022","journal-title":"Cells"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1002\/jbm.b.35243","article-title":"Type H blood vessels in coupling angiogenesis-osteogenesis and its application in bone tissue engineering","volume":"111","author":"Xu","year":"2023","journal-title":"J Biomed Mater Res B Appl Biomater"},{"key":"B10","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1210\/endrev\/bnac008","article-title":"Fracture healing in the setting of endocrine diseases, aging, and cellular senescence","volume":"43","author":"Saul","year":"2022","journal-title":"Endocr Rev"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24043772","article-title":"Oxidative stress and inflammation in osteoporosis: molecular mechanisms involved and the relationship with microRNAs","volume":"24","author":"Iantomasi","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B12","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1093\/rheumatology\/keh344","article-title":"Osteoarthritis, angiogenesis and inflammation","volume":"44","author":"Bonnet","year":"2005","journal-title":"Rheumatology (Oxford)"},{"key":"B13","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1038\/s41591-018-0020-z","article-title":"Targeting skeletal endothelium to ameliorate bone loss","volume":"24","author":"Xu","year":"2018","journal-title":"Nat Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/4974343","article-title":"Curcumin prevents diabetic osteoporosis through promoting osteogenesis and angiogenesis coupling via NF-\u03baB signaling","volume":"2022","author":"Fan","year":"2022","journal-title":"Evid Based Complement Alternat Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000034773","article-title":"Mechanism of Liuwei Dihuang Pills in treating osteoporosis based on network pharmacology","volume":"102","author":"Wang","year":"2023","journal-title":"Medicine"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-021-02178-z","article-title":"STAT3 activation by catalpol promotes osteogenesis-angiogenesis coupling, thus accelerating osteoporotic bone repair","volume":"12","author":"Chen","year":"2021","journal-title":"Stem Cell Res Ther"},{"key":"B17","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.jep.2018.01.007","article-title":"Bu-Shen-Tong-Luo decoction prevents bone loss via inhibition of bone resorption and enhancement of angiogenesis in ovariectomy-induced osteoporosis of rats","volume":"220","author":"Yuan","year":"2018","journal-title":"J Ethnopharmacol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/5576023","article-title":"Senescence osteoblast-derived exosome-mediated miR-139-5p regulates endothelial cell functions","volume":"2021","author":"Lu","year":"2021","journal-title":"Biomed Res Int"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/cbf.2911","article-title":"VEGF and bone cell signalling: an essential vessel for communication","volume":"31","author":"Clarkin","year":"2013","journal-title":"Cell Biochem Funct"},{"key":"B20","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1007\/s00005-014-0285-y","article-title":"Distinct VEGF functions during bone development and homeostasis","volume":"62","author":"Liu","year":"2014","journal-title":"Arch Immunol Ther Exp (Warsz)"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1016\/j.cell.2019.01.021","article-title":"VEGF in signaling and disease: beyond discovery and development","volume":"176","author":"Apte","year":"2019","journal-title":"Cell"},{"key":"B22","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/nature13146","article-title":"Endothelial Notch activity promotes angiogenesis and osteogenesis in bone","volume":"507","author":"Ramasamy","year":"2014","journal-title":"Nature"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1002\/jcp.31042","article-title":"Osteohematology: To be or Notch to be","volume":"238","author":"Rothzerg","year":"2023","journal-title":"J Cell Physiol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s11657-019-0677-z","article-title":"Advances in the understanding of the role of type-H vessels in the pathogenesis of osteoporosis","volume":"15","author":"Ding","year":"2020","journal-title":"Arch Osteoporos"},{"key":"B25","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/nrendo.2013.154","article-title":"Wnt signalling in osteoporosis: mechanisms and novel therapeutic approaches","volume":"9","author":"Canalis","year":"2013","journal-title":"Nat Rev Endocrinol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3390\/biom13030483","article-title":"Progress of Wnt signaling pathway in osteoporosis","volume":"13","author":"Gao","year":"2023","journal-title":"Biomolecules"},{"key":"B27","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.maturitas.2014.04.013","article-title":"Wnt signaling and osteoporosis","volume":"78","author":"Manolagas","year":"2014","journal-title":"Maturitas"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201902931","article-title":"BMP-2 signaling and mechanotransduction synergize to drive osteogenic differentiation via YAP\/TAZ","volume":"7","author":"Wei","year":"2020","journal-title":"Adv Sci (Weinh)"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1236893","article-title":"Review on the protective activity of osthole against the pathogenesis of osteoporosis","volume":"14","author":"Chen","year":"2023","journal-title":"Front Pharmacol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1038\/nature13145","article-title":"Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone","volume":"507","author":"Kusumbe","year":"2014","journal-title":"Nature"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2017.00068","article-title":"It takes two to tango: coupling of angiogenesis and osteogenesis for bone regeneration","volume":"5","author":"Grosso","year":"2017","journal-title":"Front Bioeng Biotechnol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"17543","DOI":"10.1021\/acsami.2c23107","article-title":"Drug-delivery nanoplatform with synergistic regulation of angiogenesis-osteogenesis coupling for promoting vascularized bone regeneration","volume":"15","author":"Li","year":"2023","journal-title":"ACS Appl Mater Interfaces"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1359\/jbmr.090602","article-title":"Regulation of osteogenesis-angiogenesis coupling by HIFs and VEGF","volume":"24","author":"Schipani","year":"2009","journal-title":"J Bone Miner Res"},{"key":"B34","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.actbio.2022.07.014","article-title":"Robust coupling of angiogenesis and osteogenesis by VEGF-decorated matrices for bone regeneration","volume":"149","author":"Burger","year":"2022","journal-title":"Acta Biomater"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1038\/nm.3668","article-title":"PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis","volume":"20","author":"Xie","year":"2014","journal-title":"Nat Med"},{"key":"B36","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1093\/cvr\/cvn039","article-title":"Diabetes and vessel wall remodelling: from mechanistic insights to regenerative therapies","volume":"78","author":"Spinetti","year":"2008","journal-title":"Cardiovasc Res"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8823573","article-title":"Impaired angiogenesis in aging and diabetes: therapeutic potential of stem cells","volume":"2020","author":"Liu","year":"2020","journal-title":"Stem Cells Int"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0178720","article-title":"Angiogenesis impairment in diabetes: role of methylglyoxal-induced receptor for advanced glycation endproducts, autophagy and vascular endothelial growth factor receptor 2","volume":"12","author":"Hu","year":"2017","journal-title":"PLoS One"},{"key":"B39","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1038\/s41584-022-00783-7","article-title":"Next-generation imaging of the skeletal microenvironment","volume":"18","author":"Gr\u00fcneboom","year":"2022","journal-title":"Nat Rev Rheumatol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1016\/j.bone.2017.01.023","article-title":"The chronic kidney disease \u2014 mineral bone disorder (CKD-MBD): advances in pathophysiology","volume":"28","author":"Hruska","year":"2017","journal-title":"J Am Soc Nephrol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/j.kint.2019.03.019","article-title":"HIF activation against CKD: more than a renal player","volume":"96","author":"Tanaka","year":"2019","journal-title":"Kidney Int"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2019.05.019","article-title":"Deferoxamine released from calcium phosphate cement enhances angiogenesis and osteogenesis in uremic rats","volume":"213","author":"Zhang","year":"2019","journal-title":"Biomaterials"},{"key":"B43","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.jot.2019.12.004","article-title":"Guidelines for clinical diagnosis and treatment of osteonecrosis of the femoral head in adults (2019 version)","volume":"21","author":"Zhao","year":"2020","journal-title":"J Orthop Translat"},{"key":"B44","doi-asserted-by":"publisher","first-page":"426","DOI":"10.7150\/thno.34126","article-title":"Type H blood vessels in bone modeling and remodeling","volume":"10","author":"Peng","year":"2020","journal-title":"Theranostics"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2022.116347","article-title":"The diagnostic role of bone blood vessel in osteoporosis","volume":"158","author":"Al Saedi","year":"2022","journal-title":"Bone"},{"key":"B46","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1161\/CIRCRESAHA.118.312563","article-title":"Mechanisms of dysfunction in the aging vasculature and role in age-related disease","volume":"123","author":"Donato","year":"2018","journal-title":"Circ Res"},{"key":"B47","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.bone.2019.01.015","article-title":"Cellular senescence in bone","volume":"121","author":"Farr","year":"2019","journal-title":"Bone"},{"key":"B48","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1038\/s41586-021-03795-7","article-title":"Aged skeletal stem cells generate an inflammatory degenerative niche","volume":"597","author":"Ambrosi","year":"2021","journal-title":"Nature"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms16003","article-title":"MiR-497\u223c195 cluster regulates angiogenesis during coupling with osteogenesis by maintaining endothelial Notch and HIF-1\u03b1 activity","volume":"8","author":"Yang","year":"2017","journal-title":"Nat Commun"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0112744","article-title":"Dimethyloxalylglycine prevents bone loss in ovariectomized C57BL\/6J mice through enhanced angiogenesis and osteogenesis","volume":"9","author":"Peng","year":"2014","journal-title":"PLoS One"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.101956","article-title":"Targeting the vascular-bone axis in aging-related bone loss: Mechanisms and therapeutic opportunities","volume":"88","author":"Liu","year":"2023","journal-title":"Ageing Res Rev"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3390\/cells8080886","article-title":"Mesenchymal stem cells for regenerative medicine","volume":"8","author":"Han","year":"2019","journal-title":"Cells"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3390\/cells10081959","article-title":"Mesenchymal stem cell-derived exosomes: Applications in regenerative medicine","volume":"10","author":"Hade","year":"2021","journal-title":"Cells"},{"key":"B54","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.bbrc.2021.10.033","article-title":"Mesenchymal stem cells prevent ovariectomy-induced osteoporosis formation in mice through intraosseous vascular remodeling","volume":"582","author":"Wang","year":"2021","journal-title":"Biochem Biophys Res Commun"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.608521","article-title":"BMSC-derived exosomal miR-29a promotes angiogenesis and osteogenesis","volume":"8","author":"Lu","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"836","DOI":"10.7150\/ijbs.14809","article-title":"Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells repair critical-sized bone defects through enhanced angiogenesis and osteogenesis in osteoporotic rats","volume":"12","author":"Qi","year":"2016","journal-title":"Int J Biol Sci"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.826660","article-title":"Melatonin accelerates osteoporotic bone defect repair by promoting osteogenesis-angiogenesis coupling","volume":"13","author":"Zheng","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B58","doi-asserted-by":"publisher","first-page":"4422","DOI":"10.1096\/fj.201700118R","article-title":"Declining histone acetyltransferase GCN5 represses BMSC-mediated angiogenesis during osteoporosis","volume":"31","author":"Jing","year":"2017","journal-title":"FASEB J"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202001080RR","article-title":"Mechanical loading stimulates bone angiogenesis through enhancing type H vessel formation and downregulating exosomal miR-214-3p from bone marrow-derived mesenchymal stem cells","volume":"35","author":"Wang","year":"2021","journal-title":"FASEB J"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-022-01400-1","article-title":"Bone-targeting delivery of platelet lysate exosomes ameliorates glucocorticoid-induced osteoporosis by enhancing bone-vessel coupling","volume":"20","author":"Zheng","year":"2022","journal-title":"J Nanobiotechnology"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27030781","article-title":"Mechanistic basis for the role of phytochemicals in inflammation-associated chronic diseases","volume":"27","author":"Cote","year":"2022","journal-title":"Molecules"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1080\/10408398.2016.1251390","article-title":"Anti-inflammatory effects of phytochemicals from fruits, vegetables, and food legumes: A review","volume":"58","author":"Zhu","year":"2018","journal-title":"Crit Rev Food Sci Nutr"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.154558","article-title":"Antidepressant effects of the traditional Chinese herbal formula Xiao-Yao-San and its bioactive ingredients","volume":"109","author":"Wang","year":"2023","journal-title":"Phytomedicine"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.16121","article-title":"Daidzein alleviates osteoporosis by promoting osteogenesis and angiogenesis coupling","volume":"11","author":"Jia","year":"2023","journal-title":"PeerJ"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1177\/1934578X221134881","article-title":"Icariin: a potential alternative against osteoporosis","volume":"17","author":"Long","year":"2022","journal-title":"Nat Prod Commun"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-05392-z","article-title":"Evaluation of osteogenesis and angiogenesis of icariin in local controlled release and systemic delivery for calvarial defect in ovariectomized rats","volume":"7","author":"Wu","year":"2017","journal-title":"Sci Rep"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.3390\/cells11121921","article-title":"Autocrine activity of extracellular vesicles induced by icariin and its effectiveness in glucocorticoid-induced injury of bone microvascular endothelial cells","volume":"11","author":"Zhang","year":"2022","journal-title":"Cells"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3390\/nu14102106","article-title":"Sesamin promotes osteoporotic fracture healing by activating chondrogenesis and angiogenesis pathways","volume":"14","author":"Yang","year":"2022","journal-title":"Nutrients"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2022.5167","article-title":"Total flavonoids of Rhizoma Drynariae enhances CD31hi vessel formation and subsequent bone regeneration in rat models of distraction osteogenesis by activating PDGF-BB\/VEGF\/RUNX2\/OSX signaling axis","volume":"50","author":"Shen","year":"2022","journal-title":"Int J Mol Med"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.503524","article-title":"Total flavonoids of Rhizoma Drynariae enhances angiogenic-osteogenic coupling during distraction osteogenesis by promoting type H vessel formation through PDGF-BB\/PDGFR-\u03b2 instead of HIF-1\u03b1\/ VEGF axis","volume":"11","author":"Shen","year":"2020","journal-title":"Front Pharmacol"},{"key":"B71","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.cbi.2016.10.020","article-title":"Naringin promotes fracture healing through stimulation of angiogenesis by regulating the VEGF\/VEGFR-2 signaling pathway in osteoporotic rats","volume":"261","author":"Song","year":"2017","journal-title":"Chem Biol Interact"},{"key":"B72","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.3892\/ijmm.2017.3160","article-title":"Naringin inhibits vascular endothelial cell apoptosis via endoplasmic reticulum stress- and mitochondrial-mediated pathways and promotes intraosseous angiogenesis in ovariectomized rats","volume":"40","author":"Shangguan","year":"2017","journal-title":"Int J Mol Med"},{"key":"B73","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1021\/acs.jafc.2c07005","article-title":"Vitexin regulates angiogenesis and osteogenesis in ovariectomy-induced osteoporosis of rats via the VDR\/PI3K\/AKT\/eNOS signaling pathway","volume":"71","author":"Liu","year":"2023","journal-title":"J Agric Food Chem"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8412468","article-title":"Panax notoginseng saponins prevent bone loss by promoting angiogenesis in an osteoporotic mouse model","volume":"2020","author":"Hu","year":"2020","journal-title":"Biomed Res Int"},{"key":"B75","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/j.biopha.2018.10.085","article-title":"Combined treatment with cinnamaldehyde and \u03b2-TCP had an additive effect on bone formation and angiogenesis in critical size calvarial defect in ovariectomized rats","volume":"109","author":"Weng","year":"2019","journal-title":"Biomed Pharmacother"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.998971","article-title":"Modified Qing'e Pills exerts anti-osteoporosis effects and prevents bone loss by enhancing type H blood vessel formation","volume":"13","author":"Lu","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B77","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.1007\/s00018-016-2174-5","article-title":"Mechanisms of long noncoding RNA function in development and disease","volume":"73","author":"Schmitz","year":"2016","journal-title":"Cell Mol Life Sci"},{"key":"B78","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.2174\/1389450123666220919122520","article-title":"Long non-coding RNA therapeutics: Recent advances and challenges","volume":"23","author":"Sangeeth","year":"2022","journal-title":"Curr Drug Targets"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.697858","article-title":"LncRNA TCONS_00023297 regulates the balance of osteogenic and adipogenic differentiation in bone marrow mesenchymal stem cells and the coupling process of osteogenesis and angiogenesis","volume":"9","author":"Wang","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2021.12350","article-title":"lncRNA GAS5 regulates angiogenesis by targeting miR-10a-3p\/VEGFA in osteoporosis","volume":"24","author":"Wu","year":"2021","journal-title":"Mol Med Rep"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-021-00392-2","article-title":"lncRNA SNHG1 induced by SP1 regulates bone remodeling and angiogenesis via sponging miR-181c-5p and modulating SFRP1\/Wnt signaling pathway","volume":"27","author":"Yu","year":"2021","journal-title":"Mol Med"},{"key":"B82","doi-asserted-by":"publisher","first-page":"5451","DOI":"10.1002\/jcp.27486","article-title":"An overview of microRNAs: Biology, functions, therapeutics, and analysis methods","volume":"234","author":"Saliminejad","year":"2019","journal-title":"J Cell Physiol"},{"key":"B83","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1515\/hsz-2014-0268","article-title":"MicroRNA-210 is involved in the regulation of postmenopausal osteoporosis through promotion of VEGF expression and osteoblast differentiation","volume":"396","author":"Liu","year":"2015","journal-title":"Biol Chem"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2377-4","article-title":"miR-143 promotes angiogenesis and osteoblast differentiation by targeting HDAC7","volume":"11","author":"Wang","year":"2020","journal-title":"Cell Death Dis"},{"key":"B85","doi-asserted-by":"publisher","first-page":"2016","DOI":"10.1016\/j.cell.2022.04.021","article-title":"Circular RNAs: Characterization, cellular roles, and applications","volume":"185","author":"Liu","year":"2022","journal-title":"Cell"},{"key":"B86","doi-asserted-by":"publisher","first-page":"10275","DOI":"10.18632\/aging.202791","article-title":"CircRNA hsa_circ_0006215 promotes osteogenic differentiation of BMSCs and enhances osteogenesis-angiogenesis coupling by competitively binding to miR-942-5p and regulating RUNX2 and VEGF","volume":"13","author":"Ji","year":"2021","journal-title":"Aging (Albany NY)"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107821","article-title":"Expression of angiogenesis-related proteins in bone marrow mesenchymal stem cells induced by osteoprotegerin during osteogenic differentiation in rats","volume":"98","author":"Wang","year":"2021","journal-title":"Int Immunopharmacol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.596783","article-title":"The effect of MMP-2 inhibitor 1 on osteogenesis and angiogenesis during bone regeneration","volume":"8","author":"Jiang","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14076-3","article-title":"Endothelial ZEB1 promotes angiogenesis-dependent bone formation and reverses osteoporosis","volume":"11","author":"Fu","year":"2020","journal-title":"Nat Commun"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202300516","article-title":"A recombinant parathyroid hormone-related peptide locally applied in osteoporotic bone defect","volume":"10","author":"Wang","year":"2023","journal-title":"Adv Sci (Weinh)"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adg8982","article-title":"Parathyroid hormone treatment partially reverses endplate remodeling and attenuates low back pain in animal models of spine degeneration","volume":"15","author":"Ling","year":"2023","journal-title":"Sci Transl Med"},{"key":"B92","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.biomaterials.2018.06.035","article-title":"Early effects of parathyroid hormone on vascularized bone regeneration and implant osseointegration in aged rats","volume":"179","author":"Jiang","year":"2018","journal-title":"Biomaterials"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0226163","article-title":"PTH1-34 improves bone healing by promoting angiogenesis and facilitating MSCs migration and differentiation in a stabilized fracture mouse model","volume":"14","author":"Jiang","year":"2019","journal-title":"PLoS One"},{"key":"B94","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1007\/s40265-015-0419-5","article-title":"Dexmedetomidine: A review of its use for sedation in the intensive care setting","volume":"75","author":"Keating","year":"2015","journal-title":"Drugs"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119273","article-title":"Mechanism of dexmedetomidine regulating osteogenesis-angiogenesis coupling through the miR-361-5p\/VEGFA axis in postmenopausal osteoporosis","volume":"275","author":"Wang","year":"2021","journal-title":"Life Sci"},{"key":"B96","doi-asserted-by":"publisher","first-page":"2515","DOI":"10.1002\/jbm.a.35793","article-title":"Deferoxamine released from poly(lactic-co-glycolic acid) promotes healing of osteoporotic bone defect via enhanced angiogenesis and osteogenesis","volume":"104","author":"Jia","year":"2016","journal-title":"J Biomed Mater Res A"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.3390\/nu13103480","article-title":"Circadian rhythm dysregulation and restoration: The role of melatonin","volume":"13","author":"Vasey","year":"2021","journal-title":"Nutrients"},{"key":"B98","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":"B99","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1056\/NEJMoa1305224","article-title":"Romosozumab in postmenopausal women with low bone mineral density","volume":"370","author":"McClung","year":"2014","journal-title":"N Engl J Med"},{"key":"B100","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1172\/jci83731","article-title":"Efficacy of anti-sclerostin antibody BPS804 in adult patients with hypophosphatasia","volume":"32","author":"Seefried","year":"2017","journal-title":"J Bone Miner Res"},{"key":"B101","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1158\/1078-0432.CCR-15-2145","article-title":"A phase I first-in-human study of AMG 780, an anti-angiopoietin-1 and -2 monoclonal antibody, in patients with advanced solid tumors","volume":"34","author":"Papadopoulos","year":"2016","journal-title":"Invest New Drugs"},{"key":"B102","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.bbrc.2022.07.056","article-title":"Roxadustat promotes osteogenesis and angiogenesis via HIF-1\u03b1\/VEGF signaling pathway in osteoporotic fracture healing","volume":"623","author":"Li","year":"2022","journal-title":"Biochem Biophys Res Commun"},{"key":"B103","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1161\/CIRCULATIONAHA.110.985150","article-title":"Rapid, direct effects of statin treatment on arterial redox state and nitric oxide bioavailability in human atherosclerosis via tetrahydrobiopterin-mediated eNOS coupling","volume":"124","author":"Antoniades","year":"2011","journal-title":"Circulation"},{"key":"B104","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1007\/s00198-016-3844-8","article-title":"Efficacy of statins for osteoporosis: a systematic review and meta-analysis","volume":"28","author":"An","year":"2017","journal-title":"Osteoporos Int"},{"key":"B105","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.jvs.2009.07.116","article-title":"Simvastatin augments revascularization and reperfusion in a murine model of hindlimb ischemia","volume":"51","author":"Matsumoto","year":"2010","journal-title":"J Vasc Surg"},{"key":"B106","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.jconrel.2015.07.022","article-title":"Potential mechanisms and applications of statins on osteogenesis: Current modalities, conflicts and future directions","volume":"215","author":"Oryan","year":"2015","journal-title":"J Control Release"},{"key":"B107","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1002\/jor.21219","article-title":"Low dose erythropoietin stimulates bone healing in mice","volume":"29","author":"Garc\u00eda","year":"2011","journal-title":"J Orthop Res"},{"key":"B108","doi-asserted-by":"publisher","first-page":"1890","DOI":"10.1096\/fj.14-259085","article-title":"Erythropoietin directly stimulates osteoclast precursors and induces bone loss","volume":"29","author":"Hiram-Bab","year":"2015","journal-title":"FASEB J"},{"key":"B109","doi-asserted-by":"publisher","first-page":"3043","DOI":"10.1161\/01.cir.99.23.3043","article-title":"Tissue inhibition of angiotensin-converting enzyme activity stimulates angiogenesis in vivo","volume":"99","author":"Fabre","year":"1999","journal-title":"Circulation"},{"key":"B110","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1016\/j.bone.2005.09.011","article-title":"Angiotensin converting enzyme inhibitor use is associated with higher bone mineral density in elderly Chinese","volume":"38","author":"Lynn","year":"2006","journal-title":"Bone"},{"key":"B111","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1161\/ATVBAHA.107.147421","article-title":"Sildenafil promotes ischemia-induced angiogenesis through a PKG-dependent pathway","volume":"27","author":"Senthilkumar","year":"2007","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B112","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1161\/01.CIR.0000155252.23933.2D","article-title":"Sildenafil prevents endothelial dysfunction induced by ischemia and reperfusion via opening of adenosine triphosphate-sensitive potassium channels: a human in vivo study","volume":"111","author":"Gori","year":"2005","journal-title":"Circulation"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-8-49","article-title":"Pioglitazone enhances collateral blood flow in ischemic hindlimb of diabetic mice through an Akt-dependent VEGF-mediated mechanism, regardless of PPAR\u03b3 stimulation","volume":"8","author":"Biscetti","year":"2009","journal-title":"Cardiovasc Diabetol"},{"key":"B114","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1111\/jpi.12252","article-title":"Melatonin improves bone mineral density at the femoral neck in postmenopausal women with osteopenia: a randomized controlled trial","volume":"59","author":"Amstrup","year":"2015","journal-title":"J Pineal Res"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173090","article-title":"Dexmedetomidine attenuates lipopolysaccharide-induced acute lung injury by promoting angiogenesis in rats","volume":"878","author":"Li","year":"2020","journal-title":"Eur J Pharmacol"},{"key":"B116","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.ijsu.2015.11.030","article-title":"Shock wave as biological therapeutic tool: From mechanical stimulation to recovery and healing, through mechanotransduction","volume":"24","author":"d'Agostino","year":"2016","journal-title":"Int J Surg"},{"key":"B117","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s10103-016-1895-8","article-title":"Early angiogenic response to shock waves in a three-dimensional model of human microvascular endothelial cell culture (HMEC-1)","volume":"26","author":"Sansone","year":"2012","journal-title":"J Biol Regul Homeost Agents"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1038\/srep44130","article-title":"An innovative approach for enhancing bone defect healing using PLGA scaffolds seeded with extracorporeal-shock-wave-treated bone marrow mesenchymal stem cells (BMSCs)","volume":"7","author":"Chen","year":"2017","journal-title":"Sci Rep"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/1404650","article-title":"Extracorporeal shock wave rebuilt subchondral bone in vivo and activated Wnt5a\/Ca2+ signaling in vitro","volume":"2017","author":"Yu","year":"2017","journal-title":"Biomed Res Int"},{"key":"B120","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1002\/jor.20948","article-title":"Osteogenesis induced by extracorporeal shockwave in treatment of delayed osteotendinous junction healing","volume":"28","author":"Qin","year":"2010","journal-title":"J Orthop Res"},{"key":"B121","doi-asserted-by":"publisher","first-page":"2909","DOI":"10.3892\/mmr.2018.9279","article-title":"Low-intensity pulsed ultrasound promotes angiogenesis via the PI3K\/Akt signaling pathway in human umbilical vein endothelial cells","volume":"18","author":"Li","year":"2018","journal-title":"Mol Med Rep"},{"key":"B122","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.jot.2020.10.004","article-title":"LIPUS promotes endothelial cell tube formation through the ERK\/HIF-1\u03b1\/VEGF signaling pathway","volume":"25","author":"Xu","year":"2020","journal-title":"J Orthop Translat"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-025-00454-9","article-title":"Injured bone-triggered osteokines secretion promotes diabetic wound healing","volume":"13","author":"Shen","year":"2025","journal-title":"Bone Res"},{"key":"B124","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1002\/jor.24157","article-title":"Low-intensity pulsed ultrasound stimulates osteogenic differentiation of periosteal cells in vitro","volume":"37","author":"Chen","year":"2019","journal-title":"J Orthop Res"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-021-02256-2","article-title":"Exosomal circPDE4B from MSCs prevents steroid-induced osteonecrosis of femoral head by regulating osteogenesis and angiogenesis","volume":"12","author":"Chen","year":"2021","journal-title":"Stem Cell Res Ther"},{"key":"B126","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1016\/j.stem.2018.05.004","article-title":"Mesenchymal stromal cells: clinical challenges and therapeutic opportunities","volume":"22","author":"Galipeau","year":"2018","journal-title":"Cell Stem Cell"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23137167","article-title":"MicroRNA-based diagnosis and therapy","volume":"23","author":"Ho","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B128","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1111\/os.13204","article-title":"The mechanism and function of miRNA in intervertebral disc degeneration","volume":"14","author":"Wang","year":"2022","journal-title":"Orthop Surg"},{"key":"B129","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1038\/s41580-022-00566-8","article-title":"Long non-coding RNAs: definitions, functions, challenges and recommendations","volume":"24","author":"Mattick","year":"2023","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B130","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1016\/j.molcel.2018.06.034","article-title":"The biogenesis, functions, and challenges of circular RNAs","volume":"71","author":"Li","year":"2018","journal-title":"Mol Cell"},{"key":"B131","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/ijos.2012.33","article-title":"The role of vascular endothelial growth factor in ossification","volume":"4","author":"Yang","year":"2012","journal-title":"Int J Oral Sci"},{"key":"B132","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1093\/jnci\/djac071","article-title":"Skeletal toxicities of VEGF receptor tyrosine kinase inhibitors: A systematic review and meta-analysis","volume":"114","author":"Hojjati","year":"2022","journal-title":"J Natl Cancer Inst"},{"key":"B133","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.ecl.2012.04.004","article-title":"Glucocorticoid-induced osteoporosis and osteonecrosis","volume":"41","author":"Weinstein","year":"2012","journal-title":"Endocrinol Metab Clin North Am"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202203099","article-title":"Multifunctional scaffold for osteoporotic pathophysiological microenvironment improvement and vascularized bone defect regeneration","volume":"12","author":"Zhao","year":"2023","journal-title":"Adv Healthc Mater"},{"key":"B135","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1186\/bcr1269","article-title":"Aromatase inhibitors and bone health","volume":"7","author":"Bundred","year":"2005","journal-title":"Breast Cancer Res"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1790054\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T04:26:17Z","timestamp":1775535977000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1790054\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,7]]},"references-count":135,"alternative-id":["10.3389\/fendo.2026.1790054"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1790054","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,7]]},"article-number":"1790054"}}