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Cartilage‐derived morphogenetic proteins enhance the osteogenic protein‐1‐induced osteoblastic cell differentiation of C2C12 cells
Author(s) -
Yeh LeeChuan C.,
Tsai Alicia D.,
Zavala Michelle C.,
Lee John C.
Publication year - 2004
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20079
Subject(s) - c2c12 , bone morphogenetic protein 2 , osteocalcin , microbiology and biotechnology , alkaline phosphatase , chemistry , biology , myocyte , biochemistry , in vitro , myogenesis , enzyme
Previous studies have shown that osteogenic protein‐1 (OP‐1; also known as BMP‐7) induces differentiation of the pluripotent mesenchymal cell line C2C12 into osteoblastic cells. OP‐1 also alters the steady‐state levels of messenger RNA (mRNA) encoding for the cartilage‐derived morphogenetic proteins (CDMPs) in C2C12 cells. In the present study, the effects of exogenous CDMPs on bone cell differentiation induced by OP‐1 in C2C12 cells were examined. Exogenous CDMP‐1, ‐2, and ‐3 synergistically and dose‐dependently enhanced OP‐1 action in stimulating alkaline phosphatase (AP) activity and osteocalcin (OC) mRNA expression. AP staining studies revealed that the combination of OP‐1 and CDMP enhanced OP‐1 action by stimulating those cells that had responded to OP‐1 and not by activating additional cells. The combination did not change the mRNA expression of the BMPs and their receptors. CDMP‐1 enhanced the suppression of the OP‐1‐induced expression of the myogeneic differentiation regulator MyoD. CDMP‐1 and OP‐1 alone stimulated Smad5 protein expression, but the combination of OP‐1 and CDMP‐1 stimulated synergistically Smad5 protein expression. Thus, one mechanism of the observed synergy involved enhancement of the induced Smad5 protein expression. At the same protein concentration, CDMP‐1 is most potent in enhancing OP‐1 activity in inducing osteoblastic cell differentiation of C2C12 cells. CDMP‐3 is about 80% as potent as CDMP‐1, and CDMP‐2 is the least potent (about 50% of CDMP‐1). © 2004 Wiley‐Liss, Inc.