BMP-13 Emerges as a Potential Inhibitor of Bone Formation |
| |
| Authors: | Bojiang Shen Divya Bhargav Aiqun Wei Lisa A Williams Helen Tao David D F Ma and Ashish D Diwan |
| |
| Affiliation: | 1. Orthopaedic Research Institute and Department of Orthopaedic Surgery, St George Hospital, University of New South Wales, Sydney, Australia;2. Blood Stem Cell and Cancer Research Unit, Department of Haematology, St. Vincent''s Hospital Sydney, University of New South Wales, Sydney, Australia |
| |
| Abstract: | 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 |
|
|
