Sclerostin Mediates Bone Response to Mechanical Unloading Through Antagonizing Wnt/β‐Catenin Signaling |
| |
| Authors: | Chuwen Lin Xuan Jiang Zhongquan Dai Xizhi Guo Tujun Weng Jun Wang Yinghui Li Guoyin Feng Xiang Gao PhD Lin He PhD |
| |
| Affiliation: | 1. Bio‐X Center, Key Laboratory of Developmental Genetics and Neuropsychiatric Diseases, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China;2. Model Animal Research Center, MOE Key Laboratory of Model Animal for Disease Studies, Nanjing University, Nanjing, China;3. Institute for Nutritional Sciences, SIBS, Chinese Academy of Sciences, Shanghai, China;4. These authors contributed equally to this work;5. Laboratory of Space Cell and Molecular Biology, China Astronaut Research and Training Center, Beijing, China;6. Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing, China;7. Orthopaedic Institute of PLA, Xijing Hospital, the Fourth Military Medical University, Xi'an, China;8. Institutes of Biomedical Sciences Fudan University, Shanghai, China |
| |
| 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. |
| |
| Keywords: | sclerostin Wnt/β ‐catenin signaling bone mechanical unloading mechanotransduction |
|
|
