Chondrocyte Primary Cilia Lengthening and Shortening in Response to Osteoarthritic Sequelae; a Role for Integrin Alpha 1 Beta 1 and Focal Adhesions
Integrin α1β1 protects against osteoarthritis when it is upregulated in the early stages of disease, however, the mechanism behind this is currently unknown. In this thesis we investigate interplay between integrin α1β1, the cilium, and focal adhesions. We measured cilia length and F-actin peaks on ex vivo chondrocytes in wild type and itga1-null mice exposed to hypo-osmotic stress, IL-1 and TGFβ alone or in combination, and with or without FAKi. We show that integrin α1β1 and focal adhesions are necessary for cilial lengthening and increases in F-actin peaks with hypo-osmotic stress and IL-1, but not required for cilial shortening with TGFβ. In addition, we show that cilia have a maximum, resting, and minimum length, the latter corresponding to the thickness of the pericellular matrix. Through understanding the role of integrin α1β1 and cilia in chondrocyte response to osteoarthritic sequelae, their roles as potential pharmaceutical targets for osteoarthritis can be established.