Targeting subchondral bone mesenchymal stem cell activities for intrinsic joint repair in osteoarthritis

Osteoarthritis (OA) is a common age-related disease with complex pathophysiology. It is characterized by wide-ranging tissue damage and ultimate biomechanical failure of the whole joint. However, signs of tissue adaptation and attempted repair responses are evident in OA-affected osteochondral tissues. Highlighted in this review article is the role of bone-resident mesenchymal stem cells (MSCs) in these bone remodeling responses, and a proposal that targeting MSC activities in OA subchondral bone could represent a novel approach for intrinsic joint regeneration in OA. The development of these therapies will require better understanding of MSC proliferation, migration and differentiation patterns in relation to OA tissue damage and further clarification of the molecular signaling events in these MSCs during disease progression. Lay abstract: Osteoarthritis (OA) is a joint disorder, in which the cartilage, the underlying bone and other joint tissues are affected. Recent evidence demonstrating attempted repair responses in these OA tissues challenges the traditional view of OA as a degenerative disorder. Signs of tissue regeneration are particularly evident in the bone located directly underneath the damaged cartilage, where increased stem cell activity has been observed. Targeting these stem cells could represent a novel approach for intrinsic joint regeneration in OA. To progress with developing these novel therapies, a better understanding of stem cell function in normal and OA joint tissues is needed.