Chondrocyte primary cilia lengthening and shortening in response to mediators of osteoarthritis; a role for integrin α1β1 and focal adhesions

Objective: Integrin alpha 1 beta 1 protects against osteoarthritis when it is upregulated in the early stages of disease, however, the mechanism behind this is currently unknown. Hypo-osmotic stress, interleukin-1 (IL-1) and transforming growth factor beta (TGF beta) influence chondrocyte signaling and are important mediators of osteoarthritis. Evidence for primary cilia as a signaling hub for these factors and the involvement of the F-actin cytoskeleton in this response is growing. The purpose of this study was to investigate the role of integrin alpha 1 beta 1 in the response of primary cilia and the F-actin cytoskeleton to these osteoarthritic mediators. Design:Primary cilia length and the number of F-actin peaks were measured in ex vivo wild type and itga1-null chondrocytes in response to hypo-osmotic stress, IL-1, and TGF beta alone or in combination, and with or without focal adhesion kinase inhibitor. Results: We show that integrin alpha 1 beta 1 and focal adhesions are necessary for cilial lengthening and increases in Factin peaks with hypo-osmotic stress and IL-1, but are not required for cilial shortening with TGF beta. Furthermore, we established that the chondrocyte primary cilium has a resting length of 2.4 mu m, a minimum length of 2.1 mu m corresponding to the thickness of the pericellular matrix, and a maximum length of 3.0 mu m. Conclusions: While integrin alpha 1 beta 1 is not necessary for the formation of chondrocyte primary cilia and cilial shortening in response to TGF beta, it is necessary for the mediation of cilial lengthening and the formation of F-actin peaks in response to hypo-osmotic stress and IL-1.