The brain-joint axis: links between osteoarthritis and neurodegenerative disorders in aging

Osteoarthritis (OA) and neurodegenerative disorders such as Alzheimer's and Parkinson's diseases are prevalent age-related conditions that severely impair quality of life in the elderly. Growing evidence suggests shared pathological drivers, including chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, and cellular senescence, link the degeneration of articular cartilage with neuronal loss in the aging brain.

This review introduces and defines the emerging concept of the "brain-joint axis" as a bidirectional communication network integrating neural, endocrine, and immune signaling between the central nervous system (CNS) and joint tissues. By consolidating evidence of systemic crosstalk between OA and neurodegenerative disorders, we highlight how aging-related biological processes simultaneously influence joint and brain homeostasis.

We discuss how proinflammatory cytokines (e.g., interleukin-1β, tumor necrosis factor-α) and metabolic stress mediators propagate systemic inflammation that exacerbates both cartilage degradation and neuronal damage. Furthermore, we propose that OA is not merely a localized musculoskeletal disorder but part of a broader systemic neuro-immuno-endocrine network whose dysfunction contributes to neurodegeneration. Indeed, this work delineates the mechanistic framework of the brain-joint axis, emphasizing its translational potential as a therapeutic target to simultaneously mitigate OA progression and neurodegenerative decline.