{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:30:52Z","timestamp":1791275452440,"version":"4.1.0"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,6,29]]},"abstract":"\n Bone healing requires a complex interaction of growth factors that establishes an environment for efficient bone regeneration. Among these, FGFs have been considered important for intrinsic bone-healing capacity. In this study, we analyzed the role of\n Fgf-9<\/jats:italic>\n in long bone repair. One-millimeter unicortical defects were created in tibias of\n \n Fgf-9\n +\/\u2212<\/jats:sup>\n <\/jats:italic>\n and wild-type mice. Histomorphometry revealed that half-dose gene of\n Fgf-9<\/jats:italic>\n markedly reduced bone regeneration as compared with wild-type. Both immunohistochemistry and RT-PCR analysis revealed markedly decreased levels of proliferating cell nuclear antigen (PCNA), Runt-related transcription factor 2 (Runx2), osteocalcin, Vega-a, and platelet endothelial cell adhesion molecule 1 (PECAM-1) in\n \n Fgf-9\n +\/\u2212<\/jats:sup>\n <\/jats:italic>\n defects. \u03bcCT angiography indicated dramatic impairment of neovascularization in\n \n Fgf-9\n +\/\u2212<\/jats:sup>\n <\/jats:italic>\n mice as compared with controls. Treatment with FGF-9 protein promoted angiogenesis and successfully rescued the healing capacity of\n \n Fgf-9\n +\/\u2212<\/jats:sup>\n <\/jats:italic>\n mice. Importantly, although other pro-osteogenic factors [\n Fgf-2<\/jats:italic>\n ,\n Fgf-18<\/jats:italic>\n , and bone morphogenic protein 2 (\n Bmp-2<\/jats:italic>\n )] still were present in\n \n Fgf-9\n +\/\u2212<\/jats:sup>\n <\/jats:italic>\n mice, they could not compensate for the haploinsufficiency of the\n Fgf-9<\/jats:italic>\n gene. Therefore, endogenous\n Fgf-9<\/jats:italic>\n seems to play an important role in long bone repair. Taken together our data suggest a unique role for\n Fgf-9<\/jats:italic>\n in bone healing, presumably by initiating angiogenesis through Vegf-a. Moreover, this study further supports the embryonic phenotype previously observed in the developing limb, thus promoting the concept that healing processes in adult organisms may recapitulate embryonic skeletal development.\n <\/jats:p>","DOI":"10.1073\/pnas.1003317107","type":"journal-article","created":{"date-parts":[[2010,6,15]],"date-time":"2010-06-15T00:19:00Z","timestamp":1276561140000},"page":"11853-11858","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":134,"title":["Fgf-9<\/i>\n is required for angiogenesis and osteogenesis in long bone repair"],"prefix":"10.1073","volume":"107","author":[{"given":"Bj\u00f6rn","family":"Behr","sequence":"first","affiliation":[{"name":"Children's Surgical Research Program, Department of Surgery and"},{"name":"BG-Unfallklinik Ludwigshafen, Department of Plastic and Hand Surgery, University of Heidelberg, Heidelberg 39120, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Leucht","sequence":"additional","affiliation":[{"name":"Children's Surgical Research Program, Department of Surgery and"},{"name":"Department of Orthopedic Surgery, Stanford University School of Medicine, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Longaker","sequence":"additional","affiliation":[{"name":"Children's Surgical Research Program, Department of Surgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalina","family":"Quarto","sequence":"additional","affiliation":[{"name":"Children's Surgical Research Program, Department of Surgery and"},{"name":"Department of Structural and Functional Biology, University of Naples Federico II, Complesso M. 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