SMURF2 regulates bone homeostasis by disrupting SMAD3 interaction with vitamin D receptor in osteoblasts
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Author
Xu, Zhan
Greenblatt, Matthew B.
Yan, Guang
Feng, Heng
Sun, Jun
Lotinun, Sutada
Brady, Nicholas
Glimcher, Laurie H.
Zou, Weiguo
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https://doi.org/10.1038/ncomms14570Metadata
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Xu, Zhan, Matthew B. Greenblatt, Guang Yan, Heng Feng, Jun Sun, Sutada Lotinun, Nicholas Brady, Roland Baron, Laurie H. Glimcher, and Weiguo Zou. 2017. “SMURF2 regulates bone homeostasis by disrupting SMAD3 interaction with vitamin D receptor in osteoblasts.” Nature Communications 8 (1): 14570. doi:10.1038/ncomms14570. http://dx.doi.org/10.1038/ncomms14570.Abstract
Coordination between osteoblasts and osteoclasts is required for bone health and homeostasis. Here we show that mice deficient in SMURF2 have severe osteoporosis in vivo. This low bone mass phenotype is accompanied by a pronounced increase in osteoclast numbers, although Smurf2-deficient osteoclasts have no intrinsic alterations in activity. Smurf2-deficient osteoblasts display increased expression of RANKL, the central osteoclastogenic cytokine. Mechanistically, SMURF2 regulates RANKL expression by disrupting the interaction between SMAD3 and vitamin D receptor by altering SMAD3 ubiquitination. Selective deletion of Smurf2 in the osteoblast lineage recapitulates the phenotype of germline Smurf2-deficient mice, indicating that SMURF2 regulates osteoblast-dependent osteoclast activity rather than directly affecting the osteoclast. Our results reveal SMURF2 as an important regulator of the critical communication between osteoblasts and osteoclasts. Furthermore, the bone mass phenotype in Smurf2- and Smurf1-deficient mice is opposite, indicating that SMURF2 has a non-overlapping and, in some respects, opposite function to SMURF1.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321737/pdf/Terms of Use
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http://nrs.harvard.edu/urn-3:HUL.InstRepos:32071953
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