BMP-13 Emerges as a Potential Inhibitor of Bone Formation

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.

Biocompatibility and osteoconductivity of injectable bone xenograft, hydroxyapatite and hydroxyapatite-chitosan on osteoblast culture

“…The highest calcium deposition was shown on 1% of IHA at day 7 followed by 1% IHA-C and 1% of IBX (p > 0.05). Similar finding reported by Carnes et al 17 and Shen et al, 18 showing that early calcium deposition in osteoblast cell culture reached at day 7. Therefore, this result proved that all form of injectable pastes have the ability to increase mineralization of osteoblast cell in bone regeneration process.…”

“…Mineralized nodules were stained with silver nitrate solution according to the von Kossa method as described. 17 The results were statistically analyzed by ANOVA for normal data and Mann Whitney for abnormal data. P value of < 0.05 represented a significant difference.…”

Significance of soluble growth factors in the chondrogenic response of human umbilical cord matrix stem cells in a porous three dimensional scaffold

“…In vitro chondrogenesis of hUCMSC marrow stem cells Shen et al, 2008) and both growth factors act by distinct mechanisms to promote in vitro differentiation to cartilage. When used in combination, both the pathways might have been activated and resulted in enhanced chondrogenesis.…”

Localization of bone morphogenetic protein 13 in human intervertebral disc and its molecular and functional effects in vitro in 3D culture

“…This is because BMP-13 reduces the risk of bone formation by inhibiting the expression of both early and late osteogenic differentiation markers in vitro. 3 The aim of the present study was to further characterize the function of BMP-13 in human IVD cells by (1) examining the expression of BMP-13 in human scoliotic and degenerate tissue, (2) evaluating the molecular and functional effects of BMP-13 on human derived NP, AF and EP cells in vitro in 3D culture by analyzing changes in PG accumulation and protein expression of chondrocytic markers and finally (3) studying cellular migration induced by BMP-13 in vitro. …”

“…The effect of BMPs on degenerate IVDs in vitro and in vivo has been extensively studied, 2 however, the role of BMP-13 in disc regeneration has not been explored. BMP-13, the human homologue of murine growth and differentiation factor 6,3 has been highly associated with the stimulation of ECM production. BMP-13 induced aggrecan gene expression and proteoglycan (PG) synthesis in mouse mesenchymal cell line 4 and human articular chondrocytes.…”