In silico Investigation of Sex-Specific Osteoarthritis in Human Articular Chondrocytes

Abstract Osteoarthritis (OA), a progressive degenerative disease of cartilage in joints, is the most common cause chronic disability older adults. While OA mostly considered an age-related pathology, women have 1.5-fold higher risk developing relative to men and experience more severe symptoms. Yet, they remain underrepresented musculoskeletal research clinical trials. Responsible for formation, articular chondrocytes physiological changes OA, but functional implications such alterations largely unexplored due difficulties acquiring data experimentally. Through reparameterization, we expand mathematical chondrocyte model investigate sex-specific pathogenesis. We performed sensitivity analysis address impact ion channel activity healthy populations. Simulations show that female chondrocytes, resting membrane potential depolarized than male suggesting emergent differences chondrocytes. In both sexes, sensitive