Myostatin (GDF-8) inhibits chondrogenesis and chondrocyte proliferation in vitro by suppressing Sox-9 expression

Moataz Elkasrawy, Sadanand Fulzele, Matthew Bowser, Karl Wenger, Mark Hamrick

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Here, we investigate a possible direct role for myostatin in chondrogenesis. First, we examined the effects of myostatin on the proliferation of bone marrow stromal cells (BMSCs) and epiphyseal growth plate (EGP) chondrocytes (EGPCs) isolated from myostatin-deficient mice. Results show that myostatin deficiency is associated with a significant (P < 0.001) increase in proliferation of both BMSCs (+25%) and EGPCs (+35%) compared with wild-type cells. Next, we examined the effects of myostatin treatment on chondrogenic differentiation of BMSCs. These experiments show that myostatin treatment starting at either 0 or 48 h induces a significant decrease in collagen type II protein synthesis by 31% (P < 0.001) and 25% (P < 0.05), respectively. Real-time PCR reveals significant (P < 0.01) down regulation of Sox9 mRNA expression with 10 and 100 ng/ml treatments. Together, these findings suggest that myostatin has direct effects on chondrogenesis, and may, therefore, represent a potential therapeutic target for improving bone repair.

Original languageEnglish (US)
Pages (from-to)253-262
Number of pages10
JournalGrowth Factors
Volume29
Issue number6
DOIs
StatePublished - Dec 2011

Keywords

  • Bone marrow stem cells
  • Endochondral ossification
  • TGF-beta

ASJC Scopus subject areas

  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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