【摘 要】
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Fibroblast growth factor receptors 3 (FGFR3) is one of a family of 4 membrane bound receptor tyrosine kinases (FGFR1-4).FGFR3 is a negative regulator of bone development.The gain-of-function mutationo
【机 构】
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State Key Laboratory of Trauma, Burns and Combined Injury, Center of Bone Metabolism and Repair, Tra
【出 处】
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3rd International Conference on Fibroblast Growth Factors (F
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Fibroblast growth factor receptors 3 (FGFR3) is one of a family of 4 membrane bound receptor tyrosine kinases (FGFR1-4).FGFR3 is a negative regulator of bone development.The gain-of-function mutationof FGFR3 can lead to three chondrodysplasia syndromes including achondroplasia (ACH), hypochondroplasia (HCH) and thanatophoric dysplasia (TD).There have been many studies on the role of FGFR3 in chondrogenesis, however, the role of FGFR3 in bone formation is still elusive.In this study, we used mouse model with osteoblast-specific gain-of-function mutation of FGFR3 (FGFR3K644E;Oc-cre, mutant) to explore the direct effect of FGFR3 on osteoblasts function and bone formation.Both wild-type and mutant mice were observed for their body weight, body size and tail length.Histological sections of newborn mice tibiae were stained for safranine-fast green to observe the growth plate morphology.Histomorphometric analyses was used to analyze bone formation.qRT-PCR was used to evaluate the mRNA expression levels of osteogenic markers.Primary mouse calvarial cells was used to examine the differentiation and mineralization of osteoblasts.We also used TRAP staining to evaluate osteoclastogenesis in vivo.We found that adult mutant mice had decreased body size and body weight.Althougn the growth plate of newborn mice showed no observable abnormalities.Morphology analyses showed reduced trabecular number, thickness and defects in bone mineralization and bone formation.We further evaluated the ability of differentiation and mineralization of osteblasts.The differentiation of osteoblasts in mutant mice was promoted, however the mineralization was impaired.The expression levels of osteogenic markers such as Cbfal, OP and OC were up-regulated.However, there was no significant change in the formation and absorptive function of osteoclasts in mutant mice.The results suggested that gain-of-function mutation in FGFR3 in osteoblast led to impaired bone formation.
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