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, 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.

Shen B ，Wei A ，Whittaker S ，Williams LA ，Tao H ，Ma DD ，Diwan AD ... -  《-》

Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells (MSCs) in different hydrogels: influence of collagen type II extracellular matrix on MSC chondrogenesis.

Bosnakovski D ，Mizuno M ，Kim G ，Takagi S ，Okumura M ，Fujinaga T ... -  《BIOTECHNOLOGY AND BIOENGINEERING》

Comparison of multipotent differentiation potentials of murine primary bone marrow stromal cells and mesenchymal stem cell line C3H10T1/2.

Zhao L ，Li G ，Chan KM ，Wang Y ，Tang PF ... -  《-》

BMP-2 enhances TGF-beta3-mediated chondrogenic differentiation of human bone marrow multipotent mesenchymal stromal cells in alginate bead culture.

Shen B ，Wei A ，Tao H ，Diwan AD ，Ma DD ... -  《-》

BMP2 initiates chondrogenic lineage development of adult human mesenchymal stem cells in high-density culture.

Schmitt B ，Ringe J ，Häupl T ，Notter M ，Manz R ，Burmester GR ，Sittinger M ，Kaps C ... -  《DIFFERENTIATION》