RRC ID 18899
Author Watanabe-Takano H, Takano K, Keduka E, Endo T.
Title M-Ras is activated by bone morphogenetic protein-2 and participates in osteoblastic determination, differentiation, and transdifferentiation.
Journal Exp Cell Res
Abstract The small GTPase M-Ras is highly expressed in the central nervous system and plays essential roles in neuronal differentiation. However, its other cellular and physiological functions remain to be elucidated. Here, we clarify the novel functions of M-Ras in osteogenesis. M-Ras was prominently expressed in developing mouse bones particularly in osteoblasts and hypertrophic chondrocytes. Its expression was elevated in C3H/10T1/2 (10T1/2) mesenchymal cells and in MC3T3-E1 preosteoblasts during differentiation into osteoblasts. Treatment of C2C12 skeletal muscle myoblasts with bone morphogenetic protein-2 (BMP-2) to bring about transdifferentiation into osteoblasts also induced M-Ras mRNA and protein expression. Moreover, the BMP-2 treatment activated the M-Ras protein. Stable expression of the constitutively active M-Ras(G22V) in 10T1/2 cells facilitated osteoblast differentiation. M-Ras(G22V) also induced transdifferentiation of C2C12 cells into osteoblasts. In contrast, knockdown of endogenous M-Ras by RNAi interfered with osteoblast differentiation in 10T1/2 and MC3T3-E1 cells. Osteoblast differentiation in M-Ras(G22V)-expressing C2C12 cells was inhibited by treatment with inhibitors of p38 MAP kinase (MAPK) and c-Jun N-terminal kinase (JNK) but not by inhibitors of MAPK and ERK kinase (MEK) or phosphatidylinositol 3-kinase. These results imply that M-Ras, induced and activated by BMP-2 signaling, participates in the osteoblastic determination, differentiation, and transdifferentiation under p38 MAPK and JNK regulation.
Volume 316(3)
Pages 477-90
Published 2010-2-1
DOI 10.1016/j.yexcr.2009.09.028
PII S0014-4827(09)00418-2
PMID 19800879
MeSH Adipocytes / cytology Adipocytes / drug effects Adipocytes / metabolism Animals Bone Morphogenetic Protein 2 / pharmacology* Bone and Bones / cytology Bone and Bones / drug effects Bone and Bones / metabolism Cell Differentiation / drug effects* Cell Transdifferentiation / drug effects* Gene Expression Regulation / drug effects Gene Knockdown Techniques Humans JNK Mitogen-Activated Protein Kinases / metabolism Mice Monomeric GTP-Binding Proteins / genetics Monomeric GTP-Binding Proteins / metabolism* Osteoblasts / cytology* Osteoblasts / drug effects Osteoblasts / enzymology* RNA, Messenger / genetics RNA, Messenger / metabolism p38 Mitogen-Activated Protein Kinases / metabolism ras Proteins
IF 3.383
Times Cited 25
Human and Animal Cells MC3T3-E1(RCB1126)