Different endogenous threshold levels of Fibroblast Growth Factor-ligands determine the healing potential of frontal and parietal bones.
In the skull vault, neural crest derived frontal bones have an increased healing capacity and higher expression levels of Fibroblast Growth Factor-ligands as compared to mesoderm-derived parietal bones. Thus, we asked whether Fibroblast Growth Factor-ligands are responsible for the superior healing potential of frontal bones. Parietal defects in juvenile and adult mice treated with Fibroblast Growth Factor-2, -9 and -18 showed increased bone regeneration, comparable to frontal defects. Immunohistochemistry revealed increased recruitment of osteoprogenitors and activation of FGF-signaling pathways in FGF-treated parietal defects. Conversely, calvarial defects in Fgf-9(+/-) and Fgf-18(+/-) mice showed impaired calvarial healing which could be rescued by exogenous Fibroblast Growth Factor-ligands. Moreover, by utilizing Wnt1Cre/R26R mice, the migration and contribution of dura mater and pericranium cells to calvarial healing could be demonstrated. Taken together our results demonstrated that different endogenous threshold levels of Fibroblast Growth Factor-ligands in frontal and parietal bones have a profound impact on calvarial regeneration. The present study thereby opens new avenues for translational medicine.
Behr
Björn
B
Children's Surgical Research Program, Department of Surgery Stanford University School of Medicine, Stanford, CA, USA.
Panetta
Nicholas J
NJ
Longaker
Michael T
MT
Quarto
Natalina
N
D000818:Animals; D001861:Bone Regeneration / Q000502:physiology; D002454:Cell Differentiation; D049109:Cell Proliferation; D051525:Fibroblast Growth Factor 9 / Q000172:deficiency / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000172:deficiency / Q000378:metabolism*; D005624:Frontal Bone / Q000000981:diagnostic imaging / Q000473:pathology*; D008024:Ligands; D051379:Mice; D009432:Neural Crest / Q000166:cytology; D010012:Osteogenesis / Q000502:physiology; D010294:Parietal Bone / Q000000981:diagnostic imaging / Q000473:pathology*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D014057:Tomography, X-Ray Computed; D014945:Wound Healing
C496460:Fgf9 protein, mouse; D051525:Fibroblast Growth Factor 9; D008024:Ligands; C113569:fibroblast growth factor 18; D005346:Fibroblast Growth Factors