Deletion of β1 integrins from cortical osteocytes reduces load-induced bone formation

Since integrins were first described as cell adhesion receptors over two decades ago, our understanding of their binding specificity and functional capacity has evolved dramatically. A number of in vitro cell culture experiments have suggested that integrins may play a role in the response of bone cells to mechanical stimuli. To determine whether the loss of integrins in bone cells affects mechanical adaptation in vivo, we used an ulnar loading model in mice with an osteocyte-specific β1 integrin deficiency. Using a Cre-loxP strategy in which Cre was driven by the 2.3 kb ColI(α1) promoter, the β1 integrin subunit was deleted from cortical osteocytes in mature (16 week old) mice. While there was no observable skeletal phenotype as a result of β1 integrin deletion, we found that conditional knockout mice exhibited a significant reduction in bone formation rates at the ulnar midshaft in response to three consecutive days of cyclic loading compared to floxed control mice. Further, there was a greater increase in periosteal expansion in control vs. conditional knockout mice in response to loading. While there are likely multiple signaling pathways involved in the cellular response to physical stimuli, our results suggest that β1 integrins play a role in mechanically induced bone formation.