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BMP‐2 promotes differentiation of osteoblasts and chondroblasts in Runx2 ‐deficient cell lines

BMP‐2 promotes differentiation of osteoblasts and chondroblasts in Runx2 ‐deficient cell lines To investigate the molecular mechanism underlying the differentiation of osteoblasts and chondroblasts, we established a clonal cell lines, RD‐C6, from Runx2‐deficient mouse embryos. RD‐C6 cells expressed almost undetectable levels of phenotypes related to osteoblast and chondroblast differentiation at basal culture condition, whereas treatment with recombinant human bone morphogenetic protein‐2 (rhBMP‐2) or transduction of BMP‐2 by adenovirus effectively induced this cell line to express mRNA related to the differentiation of osteoblasts and chondroblasts including alkaline phosphatase, osteocalcin, and osterix. Transduction of Runx2 also induced the expression of these mRNA in RD‐C6 cells. BMP‐2 transduction increased expression levels of mRNA for Msx2 and Dlx5, but Runx2 transduction induced no significant increases in expression levels of these mRNA. Microarray analysis using RD‐C6 cells with or without rhBMP‐2 treatment demonstrated that BMP‐2 upregulated 66 genes including 13 transcription‐related molecules such as Id1, Id2, Id4, Hey1, Smad6, Smad7, and Msx2. To confirm bone and cartilage formation ability of RD‐C6 cells, we transplanted RD‐C6 cells into the peritoneal cavity of athymic mice using diffusion chambers with rhBMP‐2. RD‐C6 cells generated unmineralized cartilage but not bone. These results indicate that BMP‐2 induces Runx2‐deficient cells to express markers related to osteoblast and chondroblast differentiation using a Runx2‐independent pathway, but it failed to induce these cells to differentiate into bone‐forming osteoblasts and mature chondrocytes. J. Cell. Physiol. 211: 728–735, 2007. © 2007 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Cellular Physiology Wiley

BMP‐2 promotes differentiation of osteoblasts and chondroblasts in Runx2 ‐deficient cell lines

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References (37)

Publisher
Wiley
Copyright
Copyright © 2007 Wiley‐Liss, Inc., A Wiley Company
ISSN
0021-9541
eISSN
1097-4652
DOI
10.1002/jcp.20988
pmid
17226753
Publisher site
See Article on Publisher Site

Abstract

To investigate the molecular mechanism underlying the differentiation of osteoblasts and chondroblasts, we established a clonal cell lines, RD‐C6, from Runx2‐deficient mouse embryos. RD‐C6 cells expressed almost undetectable levels of phenotypes related to osteoblast and chondroblast differentiation at basal culture condition, whereas treatment with recombinant human bone morphogenetic protein‐2 (rhBMP‐2) or transduction of BMP‐2 by adenovirus effectively induced this cell line to express mRNA related to the differentiation of osteoblasts and chondroblasts including alkaline phosphatase, osteocalcin, and osterix. Transduction of Runx2 also induced the expression of these mRNA in RD‐C6 cells. BMP‐2 transduction increased expression levels of mRNA for Msx2 and Dlx5, but Runx2 transduction induced no significant increases in expression levels of these mRNA. Microarray analysis using RD‐C6 cells with or without rhBMP‐2 treatment demonstrated that BMP‐2 upregulated 66 genes including 13 transcription‐related molecules such as Id1, Id2, Id4, Hey1, Smad6, Smad7, and Msx2. To confirm bone and cartilage formation ability of RD‐C6 cells, we transplanted RD‐C6 cells into the peritoneal cavity of athymic mice using diffusion chambers with rhBMP‐2. RD‐C6 cells generated unmineralized cartilage but not bone. These results indicate that BMP‐2 induces Runx2‐deficient cells to express markers related to osteoblast and chondroblast differentiation using a Runx2‐independent pathway, but it failed to induce these cells to differentiate into bone‐forming osteoblasts and mature chondrocytes. J. Cell. Physiol. 211: 728–735, 2007. © 2007 Wiley‐Liss, Inc.

Journal

Journal of Cellular Physiology – Wiley

Published: Jun 1, 2007

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