BMP-13 emerges as a potential inhibitor of bone formation.
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.
Shen
Bojiang
B
Orthopaedic Research Institute, St George Hospital, University of New South Wales, Sydney, Australia. b.shen@unsw.edu.au
Bhargav
Divya
D
Wei
Aiqun
A
Williams
Lisa A
LA
Tao
Helen
H
Ma
David D F
DD
Diwan
Ashish D
AD
D000469:Alkaline Phosphatase / Q000378:metabolism; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D055431:Growth Differentiation Factor 6 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis; D016133:Polymerase Chain Reaction; D011509:Proteoglycans / Q000096:biosynthesis / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
C525718:BMP2 protein, human; C525819:BMP7 protein, human; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; C525906:GDF6 protein, human; D055431:Growth Differentiation Factor 6; D011509:Proteoglycans; D012333:RNA, Messenger; D000469:Alkaline Phosphatase