Autophagy and cartilage homeostasis mechanisms in joint health, aging and OA.

Abstract

Osteoarthritis (OA) is the most prevalent joint disease, but neither preventive measures nor disease-modifying drugs are available and a continuing need exists for safe and effective symptom-modifying therapies. Clinical trials of candidate disease-modifying OA drugs in patients with established or advanced disease have not demonstrated their efficacy, but these failed trials have motivated investigation into the mechanisms that maintain joint health. The enhancement of such mechanisms could be a novel approach to reducing the risk of OA. Aging is one of the most important risk factors for OA; however, aging of joint cartilage is a process that is distinct from the subsequent cartilage changes that develop following the onset of OA. This Review focuses on the mechanisms that maintain cell and tissue homeostasis, and how these mechanisms fail during the aging process. Autophagy is a cellular homeostasis mechanism for the removal of dysfunctional organelles and macromolecules. Defective autophagy is involved in the pathogenesis of aging-related diseases and recent observations indicate that this process is compromised in aging cartilage. Augmentation of homeostasis mechanisms is discussed as a novel avenue to delay joint aging and reduce OA risk.