Circadian Rhythm, Clock Genes and Osteoarthritis: The Dream of a Good Night's Sleep.

Abstract

Circadian rhythm is an endogenous 24-hour timing system that coordinates metabolic, inflammatory, and reparative processes required for tissue homeostasis. Disruption of this temporal organization, increasingly common because of shift work, sleep disturbance, and other modern lifestyle factors, has been implicated in chronic inflammatory and metabolic diseases, including osteoarthritis (OA). Experimental studies indicate that circadian dysregulation in joint tissues can alter chondrocyte metabolism, extracellular matrix turnover, synovial inflammatory tone, and subchondral bone remodeling. At the molecular level, perturbation of core clock components such as BMAL1, PER, and CRY is associated with oxidative stress, an imbalance between anabolism and catabolism, and increased sensitivity to inflammatory stimuli. Human evidence currently supports an association between circadian misalignment, disturbed sleep, and greater OA symptom burden, but direct causal inference remains limited. OA-related pain, reduced physical activity, and metabolic dysfunction may, in turn, aggravate sleep and circadian disruption, creating a bidirectional cycle. This review synthesizes mechanistic, animal, and human evidence on circadian regulation of joint homeostasis and discusses translational opportunities, including chronotherapy, rhythm-aligned behavioral interventions, and pharmacological modulation of clock pathways. We also highlight major limitations of the current literature and priorities for future phase-informed precision studies in OA.