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Sclerostin Mediates Bone Response to Mechanical Unloading Through Antagonizing Wnt/β‐Catenin Signaling
Author(s) -
Lin Chuwen,
Jiang Xuan,
Dai Zhongquan,
Guo Xizhi,
Weng Tujun,
Wang Jun,
Li Yinghui,
Feng Guoyin,
Gao Xiang,
He Lin
Publication year - 2009
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.090411
Subject(s) - sclerostin , wnt signaling pathway , osteoblast , mechanotransduction , downregulation and upregulation , catenin , lrp5 , beta catenin , osteoporosis , osteocyte , bone remodeling , endocrinology , microbiology and biotechnology , medicine , signal transduction , chemistry , lrp6 , wnt5a , dkk1 , biology , in vitro , gene , biochemistry
Abstract Reduced mechanical stress leads to bone loss, as evidenced by disuse osteoporosis in bedridden patients and astronauts. Osteocytes have been identified as major cells responsible for mechanotransduction; however, the mechanism underlying the response of bone to mechanical unloading remains poorly understood. In this study, we found that mechanical unloading of wildtype mice caused decrease of Wnt/β‐catenin signaling activity accompanied by upregulation of Sost. To further analyze the causal relationship among these events, Sost gene targeting mice were generated. We showed that sclerostin selectively inhibited Wnt/β‐catenin in vivo, and sclerostin suppressed the activity of osteoblast and viability of osteoblasts and osteocytes. Interestingly, Sost −/− mice were resistant to mechanical unloading‐induced bone loss. Reduction in bone formation in response to unloading was also abrogated in the mutant mice. Moreover, in contrast to wildtype mice, Wnt/β‐catenin signaling was not altered by unloading in Sost −/− mice. Those data implied that sclerostin played an essential role in mediating bone response to mechanical unloading, likely through Wnt/β‐catenin signaling. Our findings also indicated sclerostin is a promising target for preventing disuse osteoporosis.