C-type natriuretic peptide enhances osteogenic protein-1-induced osteoblastic cell differentiation via Smad5 phosphorylation

✍ Scribed by Lee-Chuan C. Yeh; Michelle C. Zavala; John C. Lee

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 185 KB
• Volume: 97
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20657

✦ Synopsis

Abstract

In the present study, we examined the hypothesis that the C‐type natriuretic peptide (CNP) enhances osteogenic protein‐1 (OP‐1) action in stimulating osteoblastic cell differentiation in primary cultures of fetal rat calvaria cell (FRC). CNP enhanced synergistically the OP‐1‐induced Alkaline Phosphatase (AP) activity and mineralized bone nodule formation in a dose‐ and time‐dependent manner. To examine possible mechanism of the synergy between OP‐1 and CNP, the expression levels of key BMP receptors and signaling molecules were examined. Western blot analysis showed that BMPR‐IB and ‐II receptor protein expression was not affected by CNP alone, but was stimulated by OP‐1 alone. The combination of OP‐1 and CNP did not further increase their protein levels. The Runx2 protein expression level was not altered by CNP alone, but was elevated by OP‐1 alone, and was slightly reduced by the combination. The Smad5 protein expression level was slightly decreased by CNP alone, but was stimulated by OP‐1 alone, and was not further stimulated by the combination. Smad5 phosphorylation was not stimulated by CNP alone, but was stimulated significantly by OP‐1 alone. The combination of OP‐1 and CNP further stimulated the OP‐1‐induced Smad5 phosphorylation. Thus, one mechanism of the observed synergy between OP‐1 and CNP involves enhancement of the Smad5 phosphorylation. J. Cell. Biochem. © 2005 Wiley‐Liss, Inc.