Studies of Post-Traumatic Osteoarthritis
Contributions to Understanding of the Role of Mechanical Forces in the Onset and Progression of Osteoarthritis
Joseph Buckwalter & James Martin
Excessive joint loadings, either single (acute contact stress) or repetitive (cumulative contact stress), cause progressive joint degeneration and subsequent development of the clinical syndrome of osteoarthritis (OA). Cumulative excessive articular surface contact stress that leads to OA results from joint dysplasia, incongruity and instability, but also may cause OA in patients without known joint abnormalities. Advances in understanding of the thresholds for mechanical damage to articular cartilage, and of the biologic mediators that cause progressive loss of articular cartilage due to excessive mechanical stress, will lead to better treatments of joint injuries and improved strategies for restoring damaged joint surfaces. Recent in vitro investigations show that reactive oxygen species (ROS) released from mitochondria following excessive articular cartilage loading can cause chondrocyte death and matrix degradation and reduce the ability of chondrocytes to respond normally to physiologic loading. Alarmins released from damaged chondrocytes trigger an inflammatory response that can cause loss of cartilage. Preventing the release of ROS or inhibiting their effects preserves chondrocytes and their matrix. Blocking the effects of Alarmins decreases the inflammatory response. Fibronectin fragments released from articular cartilage subjected to excessive loads also stimulate matrix degradation; inhibition of the molecular pathways initiated by these fragments prevents this effect. Distraction and motion of osteoarthritic articular surfaces in humans can promote joint remodeling, decrease pain and improve joint function in patients with end-stage post-traumatic OA. This result, combined with the observation that chondroprogenitor cells are active in osteoarthritic joints, suggests that altered loading creates an environment that promotes beneficial joint remodeling. Taken together, these recent advances in understanding of how mechanical forces cause loss of articular cartilage, including identification of mechanically induced mediators of cartilage loss, and of how changing joint loading can promote joint remodeling provide the basis for new biologic and mechanical approaches to the prevention and treatment of all forms of OA.