Osteoarthritis is an Inflammatory Condition
It is by now well-recognized that chronic inflammation is an important contributing cause of many common age-related diseases. Osteoarthritis is one of these, in which the maintenance of joint tissue is disrupted by unresolved inflammatory signaling. Reduction of inflammation is an important goal, but to date the interventions that can achieve this outcome are comparatively crude, a blockade of specific signal molecules that suppresses some degree of both excessive and necessary inflammatory responses. The long term side-effects of an immune system suppressed in this way are undesirable and include an increased vulnerability to pathogens. Clearance of senescent cells with senolytic therapies, removing their always-on pro-inflammatory signaling, represents the first approach to the suppression of inflammation that dampens only excess inflammation. We can hope that the future brings more such technologies.
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), or 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.