Low-Grade Inflammation in the Pathogenesis of Osteoarthritis: Cellular and Molecular Mechanisms and Strategies for Future Therapeutic Intervention

Abstract

Osteoarthritis (OA) is a musculoskeletal disease characterized by cartilage degeneration and stiffness, with chronic pain in the affected joint. It has been proposed that OA progression is associated with the development of low-grade inflammation (LGI) in the joint. In support of this principle, LGI is now recognized as the major contributor to the pathogenesis of obesity, aging, and metabolic syndromes, which have been documented as among the most significant risk factors for developing OA. These discoveries have led to a new definition of the disease, and OA has recently been recognized as a low-grade inflammatory disease of the joint. Damage-associated molecular patterns (DAMPs)/alarmin molecules, the major cellular components that facilitate the interplay between cells in the cartilage and synovium, activate various molecular pathways involved in the initiation and maintenance of LGI in the joint, which, in turn, drives OA progression. A better understanding of the pathological mechanisms initiated by LGI in the joint represents a decisive step toward discovering therapeutic strategies for the treatment of OA. Recent findings and discoveries regarding the involvement of LGI mediated by DAMPs in OA pathogenesis are discussed. Modulating communication between cells in the joint to decrease inflammation represents an attractive approach for the treatment of OA.

Targeting inflammasome-dependent mechanisms as an emerging pharmacological approach for osteoarthritis therapy

“… 4 , 5 However, increasing evidence has accumulated showing that low-grade inflammation is a critical factor driving OA pathogenesis. 6 Advanced diagnostic techniques, such as ultrasound and magnetic resonance imaging (MRI) to detect synovitis in osteoarthritic joints, set the tone for a more comprehensive understanding of inflammation in OA. 7 , 8 , 9 , 10 The presence of diverse inflammatory mediators in the synovial fluid of OA patients has strengthened the vital role of inflammation in OA pathogenesis.…”

Advances in the therapeutic application and pharmacological properties of kinsenoside against inflammation and oxidative stress-induced disorders

“…The primary histopathological alterations of osteoarthritis (OA) include articular cartilage loss, endochondral ossification, subchondral bone sclerosis, and synovial inflammation ( Terkawi et al, 2022 ; Sun Z. et al, 2022 ). Emerging evidence supports that macrophages are a critical target in OA therapy, in light of their substantial heterogeneity and plasticity properties ( Karlinsey et al, 2022 ).…”

Targeting Neuroinflammation in Osteoarthritis with Intra-Articular Adelmidrol

“…Neuro-immune signaling may occur when innate immune cells produce algogenic factors that act on the pain pathway [ 5 ]. Indeed, during OA progression, the nociceptors innervating joints can be sensitized by locally generated mediators, such as inflammatory cytokines and chemokines, nerve growth factor (NGF) [ 6 ], and disease-associated molecular patterns (DAMPs) [ 7 , 8 ] ( Figure 1 ).…”