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

• Published in: Journal of cellular biochemistry Vol. 109; no. 2; pp. 406 - 416
• Main Authors: Shen, Bojiang, Wei, Aiqun, Whittaker, Shane, Williams, Lisa A., Tao, Helen, Ma, David D.F., Diwan, Ashish D.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.02.2010
• Subjects: adipogenesis; Adipogenesis - drug effects; Adipogenesis - physiology; Alginates - pharmacology; Alginic acid; Alkaline phosphatase; Alkaline Phosphatase - metabolism; Antigens, Differentiation - physiology; Bone marrow; Bone Marrow Cells - cytology; Bone Marrow Cells - physiology; Bone morphogenetic protein 7; Bone Morphogenetic Protein 7 - metabolism; Bone Morphogenetic Protein 7 - pharmacology; Calcification, Physiologic - physiology; Calcium; Cell culture; Cell Culture Techniques; Cell Lineage; Cells, Cultured; Chondrogenesis - drug effects; Chondrogenesis - physiology; chondrogenic differentiation; Collagen (type II); Collagen (type IX); Differentiation; Gene expression; Glucuronic Acid - pharmacology; Hexuronic Acids - pharmacology; Humans; mesenchymal stromal cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - physiology; Mesenchyme; Multipotent Stem Cells - cytology; Multipotent Stem Cells - physiology; Osteocalcin; Osteogenesis - drug effects; Osteogenesis - physiology; osteogenic differentiation; Phosphoproteins; Polymerase chain reaction; Proteoglycans; Proteoglycans - biosynthesis; SOX9 Transcription Factor - physiology; stromal cells; Stromal Cells - cytology; Stromal Cells - physiology; Supplementation; Transforming Growth Factor beta3 - pharmacology; Western blotting
• ISSN: 0730-2312; 1097-4644; 1097-4644
• 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‐β3 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. © 2009 Wiley‐Liss, Inc.