title: Fgf-18 is required for osteogenesis but not angiogenesis during long bone repair.
abstract: Bone regeneration is a complex event that requires the interaction of numerous growth factors. Fibroblast growth factor (Fgf)-ligands have been previously described for their importance in osteogenesis during development. In the current study, we investigated the role of Fgf-18 during bone regeneration. By utilizing a unicortical tibial defect model, we revealed that mice haploinsufficient for Fgf-18 have a markedly reduced healing capacity as compared with wild-type mice. Reduced levels of Runx2 and Osteocalcin but not Vegfa accompanied the impaired bone regeneration. Interestingly, our data indicated that upon injury angiogenesis was not impaired in Fgf-18(+/-) mice. Moreover, other Fgf-ligands and Bmp-2 could not compensate for the loss of Fgf-18. Finally, application of FGF-18 protein was able to rescue the impaired healing in Fgf-18(+/-) mice. Thus, we identified Fgf-18 as an important mediator of bone regeneration, which is required during later stages of bone regeneration. This study provides hints on how to engineering efficiently programmed bony tissue for long bone repair.
authors: Hagey Laboratory, Department of Surgery, Stanford University School of Medicine, Stanford, California 94305, USA.
authors: Björn
authors: B
authors: Behr
authors: Michael
authors: M
authors: Sorkin
authors: Alina
authors: A
authors: Manu
authors: Marcus
authors: M
authors: Lehnhardt
authors: Michael T
authors: MT
authors: Longaker
authors: Natalina
authors: N
authors: Quarto
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects; D005346:Fibroblast Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D010641:Phenotype; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D014057:Tomography, X-Ray Computed; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects
chemical_list: D042461:Vascular Endothelial Growth Factor A; C113569:fibroblast growth factor 18; D005346:Fibroblast Growth Factors