Osteocyte β3 integrin promotes bone mass accrual and force-induced bone formation in mice

Background: Cell culture studies demonstrate the importance of β3 integrin in osteocyte mechanotransduction. However, the in vivo roles of osteocyte β3 integrin in the regulation of bone homeostasis and mechanotransduction are poorly defined. Materials and methods: To study the in vivo role of osteocyte β3 integrin in bone, we utilized the 10-kb Dmp1 (dentin matrix acidic phosphoprotein 1)-Cre to delete β3 integrin expression in osteocyte in mice. Micro-computerized tomography (μCT), bone histomorphometry and in vitro cell culture experiments were performed to determine the effects of osteocyte β3 integrin loss on bone mass accrual and biomechanical properties. In addition, in vivo tibial loading model was applied to study the possible involvement of osteocyte β3 integrin in the mediation of bone mechanotransduction. Results: Deletion of β3 integrin in osteocytes resulted in a low bone mass and impaired biomechanical properties in load-bearing long bones in adult mice. The loss of β3 integrin led to abnormal cell morphology with reduced number and length of dentritic processes in osteocytes. Furthermore, osteocyte β3 integrin loss did not impact the osteoclast formation, but significantly reduced the osteoblast-mediated bone formation rate and reduced the osteogenic differentiation of the bone marrow stromal cells in the bone microenvironment. In addition, mechanical loading failed to accelerate the anabolic bone formation in mutant mice. Conclusions: Our studies demonstrate the essential roles of osteocyte β3 integrin in regulating bone mass and mechanotransduction.