Interplay Between Integrin Alpha 1 Beta 1 and Transforming Growth Factor Beta Receptor II in the Development of Spontaneous Osteoarthritis in the Mouse Knee
Integrin α1β1 is protective against the onset on spontaneous osteoarthritis (OA), however the mechanism by which integrin α1β1 exerts this effect is unknown. In this thesis we investigated the interplay between integrin α1β1 and TβRII in spontaneous OA in the knee utilizing the itga1-null mouse. We measured behavioural responses and the histological manifestations of spontaneous OA over a period of 16 months. We show that knee cartilage degeneration and collateral ligament calcifications gradually worsened, and that pain responses increased, with increasing age, and that TβRII drives early and severe knee OA in the medial compartment of itga1-null mice. In addition, we show that the frequency of collateral ligament calcifications is greater in the medial compartment and is increased in mice with a TβRII gene deletion in cartilage. As such, this thesis further supports integrin α1β1 as a novel therapeutic target for the treatment of OA via dampened TβRII signalling.