The role of BMP-7 in chondrogenic and osteogenic differentiation of human bone marrow multipotent mesenchymal stromal cells in vitro

J Cell Biochem. 2010 Feb 1;109(2):406-16. doi: 10.1002/jcb.22412.


This study addresses the role of bone morphogenetic protein-7 (BMP-7) in chondrogenic and osteogenic differentiation of human bone marrow multipotent mesenchymal stromal cells (BM MSCs) in vitro. BM MSCs were expanded and differentiated in the presence or absence of BMP-7 in monolayer and three-dimensional cultures. After 3 days of stimulation, BMP-7 significantly inhibited MSC growth in expansion cultures. When supplemented in commonly used induction media for 7-21 days, BMP-7 facilitated both chondrogenic and osteogenic differentiation of MSCs. This was evident by specific gene and protein expression analyses using real-time PCR, Western blot, histological, and immunohistochemical staining. BMP-7 supplementation appeared to enhance upregulation of lineage-specific markers, such as type II and type IX collagens (COL2A1, COL9A1) in chondrogenic and secreted phosphoprotein 1 (SPP1), osteocalcin (BGLAP), and osterix (SP7) in osteogenic differentiation. BMP-7 in the presence of TGF-beta3 induced superior chondrocytic proteoglycan accumulation, type II collagen, and SOX9 protein expression in alginate and pellet cultures compared to either factor alone. BMP-7 increased alkaline phosphatase activity and dose-dependently accelerated calcium mineralization of osteogenic differentiated MSCs. The potential of BMP-7 to promote adipogenesis of MSCs was restricted under osteogenic conditions, despite upregulation of adipocyte gene expression. These data suggest that BMP-7 is not a singular lineage determinant, rather it promotes both chondrogenic and osteogenic differentiation of MSCs by co-ordinating with initial lineage-specific signals to accelerate cell fate determination. BMP-7 may be a useful enhancer of in vitro differentiation of BM MSCs for cell-based tissue repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis / drug effects
  • Adipogenesis / physiology*
  • Alginates / pharmacology
  • Alkaline Phosphatase / metabolism
  • Antigens, Differentiation / physiology
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / physiology
  • Bone Morphogenetic Protein 7 / metabolism*
  • Bone Morphogenetic Protein 7 / pharmacology
  • Calcification, Physiologic / physiology
  • Cell Culture Techniques
  • Cell Lineage
  • Cells, Cultured
  • Chondrogenesis / drug effects
  • Chondrogenesis / physiology*
  • Glucuronic Acid / pharmacology
  • Hexuronic Acids / pharmacology
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / physiology
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / physiology
  • Osteogenesis / drug effects
  • Osteogenesis / physiology*
  • Proteoglycans / biosynthesis
  • SOX9 Transcription Factor / physiology
  • Stromal Cells / cytology
  • Stromal Cells / physiology
  • Transforming Growth Factor beta3 / pharmacology


  • Alginates
  • Antigens, Differentiation
  • Bone Morphogenetic Protein 7
  • Hexuronic Acids
  • Proteoglycans
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • Transforming Growth Factor beta3
  • Glucuronic Acid
  • Alkaline Phosphatase