p38 mitogen-activated protein kinase regulates osteoblast differentiation through osterix.
p38 MAPK has been shown to regulate osteoblast differentiation. Inhibition of this kinase with inhibitors or dominant-negative mutant impedes osteoblast differentiation. Yet the molecular mechanism behind this regulation is not well understood. Here we provide evidence that the effect of p38 MAPK on osteoblast differentiation can be mediated by osterix (Osx), a transcription factor necessary and sufficient for osteoblast differentiation. Inhibition of p38 MAPK had minimal effects on differentiation of p53-/- osteoblasts, which had sustained Osx expression. Inhibition of p38 MAPK down-regulated the expression of Osx at both protein and mRNA levels, but not other transcription factors involved in osteoblast differentiation. More importantly, this inhibitory effect could be significantly relieved in osteoblasts overexpressing Osx. Further experiments support that Osx expression is mainly controlled by bone morphogenetic proteins existing in the culture medium, secreted by osteoblasts or provided by serum, and p38 MAPK plays a positive role in bone morphogenetic proteins-induced Osx expression. These findings identify a novel mechanism by which p38 MAPK regulates osteoblast differentiation.
Wang
Xueying
X
The Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Republic of Singapore.
Goh
Choon Hong
CH
Li
Baojie
B
D000818:Animals; D000831:Animals, Newborn; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D010006:Osteoblasts / Q000166:cytology*; D015398:Signal Transduction; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
D019485:Bone Morphogenetic Proteins; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D048051:p38 Mitogen-Activated Protein Kinases