Osteoarthritis

Osteoarthritis is a heterogeneous, whole-joint disorder and one of the leading causes of disability and premature work loss worldwide [1]. Its global burden keeps rising, and the incidence of knee osteoarthritis alone is projected to increase by roughly 75% by 2050 [2]. The disease no longer fits the older idea of simple mechanical wear, arising instead from intersecting mechanical, inflammatory, and metabolic disturbances that impair joint function [2]. It is now framed as an inflammatory process of the entire synovial joint that presents through several distinct phenotypes [3]. Obesity and previous joint injury remain the two most consistently identified and modifiable risk factors [1].

Within the cartilage, stiffening of the extracellular matrix drives chondrocytes toward senescence and accelerates tissue degeneration [4]. Because chondrocytes continuously sense and respond to mechanical loading, disrupted mechanotransduction is increasingly recognised as an early contributor to this decline [5]. The load-bearing competence of cartilage depends on its collagen and proteoglycan architecture, so matrix structure and chondrocyte response stay tightly coupled [6]. No disease-modifying osteoarthritis drug has yet been approved, and management still centres on symptom relief, exercise, weight control, and joint replacement in advanced disease [7]. This therapeutic gap has driven a shift toward phenotype-based stratification and precision-medicine strategies that match individual patients to targeted care [8].