AMPK: implications in osteoarthritis and therapeutic targets.

Osteoarthritis (OA) is the most common skeletal disease and the leading cause of pain and disability in the aged population (>65 years). However, the underlying factors involved in OA pathogenesis remain elusive which has resulted in failure to identify disease-modifying OA drugs. Altered metabolism has been shown to be a prominent pathological change in OA. As a critical bioenergy sensor, AMP-activated protein kinase (AMPK) mediates not only energy homeostasis but also redox balance in chondrocytes to counter various cell stress. Dysfunction of AMPK activity has been associated with reduced autophagy, impaired mitochondrial function, excessive reactive oxygen species generation, and inflammation in joint tissue. These abnormalities ultimately trigger articular cartilage degeneration, synovial inflammation, and abnormal subchondral bone remodeling. This review focuses on recent findings describing the central role of AMPK in joint homeostasis and OA development. We also highlight current advances that target AMPK as a novel therapeutic strategy for OA prevention.