Development of In Vitro Models of Bone-Cartilage Crosstalk

Osteoarthritis (OA) is the most common musculoskeletal disease in the western world and treatment options are currently limited. Post-traumatic osteoarthritis (PTOA) is a common subtype of the broader age-related/idiopathic OA, and results from acute injury such as anterior cruciate ligament (ACL) rupture in the knee. Joint disease has traditionally been linked exclusively with cartilage, however joint degeneration is now thought to involve other joint tissues, in particular subchondral bone. Bone-cartilage crosstalk is the interaction between cartilage and subchondral bone is thought to be a central feature of this process. Moreover, the level of communication between these tissues appears to change with the course of disease. However, the fundamental mechanisms by which changes in subchondral bone might influence changes in cartilage are not known. Thus, we sought to build an understanding of the mechanisms that maintain bone and cartilage homeostasis via communication between the two and changes in that relationship that occur during disease progression. The overall objective of the research presented in this thesis was to determine the role of subchondral bone damage in PTOA following joint injury with the development of novel in vitro bone-cartilage crosstalk model systems.