Int J Biol Sci 2009; 5(2):192-200. doi:10.7150/ijbs.5.192
Short Research Communication
BMP-13 Emerges as a Potential Inhibitor of Bone Formation
1. Orthopaedic Research Institute and Department of Orthopaedic Surgery, St George Hospital, University of New South Wales, Sydney, Australia
Bone morphogenetic protein-13 (BMP-13) plays an important role in skeletal development. In the light of a recent report that mutations in the BMP-13 gene are associated with spine vertebral fusion in Klippel-Feil syndrome, we hypothesized that BMP-13 signaling is crucial for regulating embryonic endochondral ossification. In this study, we found that BMP-13 inhibited the osteogenic differentiation of human bone marrow multipotent mesenchymal stromal cells (BM MSCs) in vitro. The endogenous BMP-13 gene expression in MSCs was examined under expansion conditions. The MSCs were then induced to differentiate into osteoblasts in osteo-inductive medium containing exogenous BMP-13. Gene expression was analysed by real-time PCR. Alkaline phosphatase (ALP) expression and activity, proteoglycan (PG) synthesis and matrix mineralization were assessed by cytological staining or ALP assay. Results showed that endogenous BMP-13 mRNA expression was higher than BMP-2 or -7 during MSC growth. BMP-13 supplementation strongly inhibited matrix mineralization and ALP activity of osteogenic differentiated MSCs, yet increased PG synthesis under the same conditions. In conclusion, BMP-13 inhibited osteogenic differentiation of MSCs, implying that functional mutations or deficiency of BMP-13 may allow excess bone formation. Our finding provides an insight into the molecular mechanisms and the therapeutic potential of BMP-13 in restricting pathological bone formation.
Keywords: BMP-13, GDF6, CDMP-2, osteogenic differentiation, mesenchymal stromal cells
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How to cite this article:
Shen B, Bhargav D, Wei A, Williams LA, Tao H, Ma DDF, Diwan AD. BMP-13 Emerges as a Potential Inhibitor of Bone Formation. Int J Biol Sci 2009; 5(2):192-200. doi:10.7150/ijbs.5.192. Available from http://www.ijbs.com/v05p0192.htm