title: Myostatin (GDF-8) inhibits chondrogenesis and chondrocyte proliferation in vitro by suppressing Sox-9 expression.
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.
authors.affiliation: Department of Cellular Biology & Anatomy, Medical College of Georgia , Georgia Health Sciences University, Augusta, USA.
authors.forename: Moataz
authors.initials: M
authors.lastname: Elkasrawy
authors.forename: Sadanand
authors.initials: S
authors.lastname: Fulzele
authors.forename: Matthew
authors.initials: M
authors.lastname: Bowser
authors.forename: Karl
authors.initials: K
authors.lastname: Wenger
authors.forename: Mark
authors.initials: M
authors.lastname: Hamrick
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D020219:Chondrogenesis / Q000187:drug effects; D006132:Growth Plate / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055435:Myostatin / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D055758:SOX9 Transcription Factor / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C525912:Mstn protein, mouse; D055435:Myostatin; D012333:RNA, Messenger; D055758:SOX9 Transcription Factor; D016212:Transforming Growth Factor beta