BMP-13 Emerges as a Potential Inhibitor of Bone Formation

<p>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 embr...

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Main Author: Bojiang Shen, Divya Bhargav, Aiqun Wei, Lisa A Williams, Helen Tao, David D F Ma, Ashish D Diwan
Format: Article
Language:English
Published: Ivyspring International Publisher 2009-01-01
Series:International Journal of Biological Sciences
Online Access:http://www.biolsci.org/v05p0192.htm
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author Bojiang Shen, Divya Bhargav, Aiqun Wei, Lisa A Williams, Helen Tao, David D F Ma, Ashish D Diwan
author_facet Bojiang Shen, Divya Bhargav, Aiqun Wei, Lisa A Williams, Helen Tao, David D F Ma, Ashish D Diwan
author_sort Bojiang Shen, Divya Bhargav, Aiqun Wei, Lisa A Williams, Helen Tao, David D F Ma, Ashish D Diwan
collection DOAJ
description <p>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.</p>
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spelling doaj.art-3c7b180cf51745ec9a3867da30c70fc32022-12-22T00:42:14ZengIvyspring International PublisherInternational Journal of Biological Sciences1449-22882009-01-0152192200BMP-13 Emerges as a Potential Inhibitor of Bone FormationBojiang Shen, Divya Bhargav, Aiqun Wei, Lisa A Williams, Helen Tao, David D F Ma, Ashish D Diwan<p>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.</p>http://www.biolsci.org/v05p0192.htm
spellingShingle Bojiang Shen, Divya Bhargav, Aiqun Wei, Lisa A Williams, Helen Tao, David D F Ma, Ashish D Diwan
BMP-13 Emerges as a Potential Inhibitor of Bone Formation
International Journal of Biological Sciences
title BMP-13 Emerges as a Potential Inhibitor of Bone Formation
title_full BMP-13 Emerges as a Potential Inhibitor of Bone Formation
title_fullStr BMP-13 Emerges as a Potential Inhibitor of Bone Formation
title_full_unstemmed BMP-13 Emerges as a Potential Inhibitor of Bone Formation
title_short BMP-13 Emerges as a Potential Inhibitor of Bone Formation
title_sort bmp 13 emerges as a potential inhibitor of bone formation
url http://www.biolsci.org/v05p0192.htm
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