Sclerostin Mediates Bone Response to Mechanical Unloading Through Antagonizing Wnt/β-Catenin Signaling

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/beta-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/beta-catenin in vivo, and sclerostin suppressed the activity of osteoblast and viability of…

• NN
  National Natural Science Foundation of China
• CA
  Chinese Academy of Sciences

  Awards: KSCX2-YW-R-01, KSCX2-YW-R
• SL
  Shanghai Leading Academic Discipline Project

  Awards: 2007CB947300, 2006BAI05A05