{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:26:17Z","timestamp":1791462377736,"version":"4.3.4"},"reference-count":58,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T00:00:00Z","timestamp":1718323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzen Municipality","doi-asserted-by":"publisher","award":["SZZYSM202108013"],"award-info":[{"award-number":["SZZYSM202108013"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274669"],"award-info":[{"award-number":["82274669"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Osthole, a natural coumarin derivative, has been shown to have multiple pharmacological activities. However, its effect on osteoporotic fracture has not yet been examined. This research was designed to explore the unknown role and potential mechanism of osthole on osteoporotic fracture healing. We first evaluated the osteogenic and angiogenic abilities of osthole. Then angiogenesis\u2010related assays were conducted to investigate the relationship between osteogenesis and angiogenesis, and further explore its molecular mechanism. After that, we established osteoporotic fracture model in ovariectomy\u2010induced osteoporosis rats and treated the rats with osthole or placebo. Radiography, histomorphometry, histology, and sequential fluorescent labeling were used to evaluate the effect of osthole on osteoporotic fracture healing. In vitro research revealed that osthole promoted osteogenesis and up\u2010regulated the expression of angiogenic\u2010related markers. Further research found that osthole couldn't facilitate the angiogenesis of human umbilical vein endothelial cells in a direct manner, but it possessed the ability to induce the osteogenesis\u2013angiogenesis coupling of bone marrow mesenchymal stem cells (BMSCs). Mechanistically, this was conducted through activating the <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.geenmedical.com\/article?id=35695863&amp;type=true\">Wnt\/\u03b2\u2010catenin<\/jats:ext-link> pathway. Subsequently, using ovariectomy\u2010induced osteoporosis tibia fracture rat model, we observed that osthole facilitated bone formation and CD31<jats:sup>hi<\/jats:sup>EMCN<jats:sup>hi<\/jats:sup> type H\u2010positive capillary formation. Sequential fluorescent labeling confirmed that osthole could effectively accelerate bone formation in the fractured region. The data above indicated that osthole could accelerate osteoporotic fracture healing by inducing the osteogenesis\u2013angiogenesis coupling of BMSCs via the Wnt\/\u03b2\u2010catenin pathway, which implied that osthole may be a potential drug for treating osteoporosis fracture.<\/jats:p>","DOI":"10.1002\/ptr.8267","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T08:40:22Z","timestamp":1718354422000},"page":"4022-4035","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Osthole accelerates osteoporotic fracture healing by inducing the osteogenesis\u2013angiogenesis coupling of BMSCs via the Wnt\/\u03b2\u2010catenin pathway"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6525-8721","authenticated-orcid":false,"given":"Sheng","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Traditional Chinese Orthopedics and Traumatology, Center for Orthopedic Surgery The Third Affiliated Hospital of Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanyu","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Orthopedics and Traumatology, Center for Orthopedic Surgery The Third Affiliated Hospital of Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0766-6051","authenticated-orcid":false,"given":"Yikai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Orthopedics and Traumatology, Center for Orthopedic Surgery The Third Affiliated Hospital of Southern Medical University  Guangzhou China"},{"name":"School of Traditional Chinese Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhua","family":"Li","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,14]]},"reference":[{"issue":"1","key":"e_1_2_9_2_1","first-page":"61","article-title":"Nanofiber scaffolds based on extracellular matrix for articular cartilage engineering: A perspective","volume":"7","author":"Ahmadian E.","year":"2023","journal-title":"Nano"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2016.01.024"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871520620666200228110704"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10133002"},{"issue":"1","key":"e_1_2_9_6_1","first-page":"19","article-title":"Biological activity of chalcones as carbonyl compound derivatives","volume":"8","author":"Binate G.","year":"2023","journal-title":"Advances in Biology & Earth Sciences"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00703"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1236893"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-021-02178-z"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.5674"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2020.05.020"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7099"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2020.03.009"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-1383(16)30003-1"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-020-3161-4"},{"issue":"3","key":"e_1_2_9_16_1","first-page":"288","article-title":"Effect of chenopodium quinoa seed extract in protecting the thylakoid membrane under the influence of cd and na salts","volume":"8","author":"Ganieva R.","year":"2023","journal-title":"Advances in Biology & Earth Sciences"},{"issue":"764","key":"e_1_2_9_17_1","first-page":"56","article-title":"Osteoporosis","volume":"18","author":"Gonzalez R. 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