Senescence in Osteoarthritis: Overview of Mechanisms and Therapeutics

Osteoarthritis is a morbid and costly condition affecting an increasingly larger segment of the population with a lack of effective treatment options. The pathophysiology of osteoarthritis is poorly understood; cell senescence is deemed to be contributory. Senescence of joint tissues particularly chondrocytes, synoviocytes (fibroblasts), and adipocytes is implicated in the pathogenesis through the production of senescence-associated proteins. Senescence-associated proteins are cytokines, matrix degradation enzymes, and chemokines that contribute to an inflammatory milieu which leads to the propagation of senescence. Senescence-modifying therapies include senolytics which eliminate senescent cells and senomorphics which inhibit the senescence-associated protein production of senescent cells. Treatments being investigated include novel agents as well as agents previously used in other conditions in rheumatology and other fields.