Regulation of skeletal cell differentiation by BMP and its inhibitor, noggin

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Coordinated interaction between signaling molecules are prerequisite for normal skeletal development. Recently, noggin was shown to interact with BMPs to inhibit their binding to receptor and has been also reported to function in cartilage morphogenesis in mammals. However, presice roles of noggin in cartilage formation and interaction beweeen noggin and BMPs during skeletogenesis were not yet to be elucidated. In this study, we examined possible roles of noggin in cartilage formation and investigated functional relationship between noggin and BMPs during skeletogenesis. Mainly two approaches were undertaken for these purposes. One is to analyze expression patterns of noggin during mouse embryogenesis and compare those or BMPs by in situ hybridization. The other is that mouse long bone organ culture was performed in vitro and noggin or BMPs protein were added to the medium or impalnted with a carrier into limb primordia to examine the effects of those proteins on long bone development. … More Noggin mRNA started to be expressed at the onset of skeletal condensation on day 11.5 dpc in cranial, appendicular and axial skeleton. The expression of noggin transcrpts persisted in cartilage until prehypertrophic stage on 15.5dpc. Exression domain of BMP7 and BMP4 transcipts are compasatory for that of noggin durig limb bone development from day 11.5dpc to 15.5dpc. Implantation of BMP7 protein inthe limb primordia of 11.5 dpc embryos induced noggin expression and this effects were not observed on 14.5 dpc limb. When isolated femur or fibula of 14.5 dpc were cultured in the presence of noggin recombinant protein. cartilage development were hampered in comparison with control. Addition of BMP7 protein in limb long bone culture resulted in overgrowth of cartilage and this effect was cancelled when noggin and BMP7 proteins were added simultaneously . These results indicate that noggin, expressed during chondrogenesis, negatively regulated cartilage development and noggin expression is induced by BMP7 in the early skeletogenesis, and suggest that noggin function as a negative signal in the negative feed back loop of BMP signaling in skeletal development. Less