The Role of BMP-7 in Chondrogenic and Osteogenic Differentiation of Human Bone Marrow Multipotent Mesenchymal Stromal Cells In Vitro

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 ion, 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 markets, 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-beta 3 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. J. Cell. Biochem. 109: 406-416, 2010. (C) 2009 Wiley-Liss, Inc.