Cellular Senescence and Inflammation in Osteoarthritis
As knowledge grows regarding the age-related accumulation of senescent cells in tissues throughout the body, researchers are establishing a role for senescent cells in many conditions already known to be characterized by the presence of chronic, unresolved inflammatory signaling. When cells become senescent, they cease to replicate and instead devote their energies to secreting inflammatory signals. As the immune system slows down in its clearance of senescent cells with age, their numbers grow and their signaling becomes constant. This is disruptive to tissue structure and function, altering the behavior of surrounding cells in harmful ways and accelerating the onset and progression of age-related conditions.
Osteoarthritis (OA) poses a significant challenge in orthopedics. Inflammatory pathways are regarded as central mechanisms in the onset and progression of OA. Growing evidence suggests that senescence acts as a mediator in inflammation-induced OA. Given the lack of effective treatments for OA, there is an urgent need for a clearer understanding of its pathogenesis. In this review, we systematically summarize the cross-talk between cellular senescence and inflammation in OA. We begin by focusing on the mechanisms and hallmarks of cellular senescence, summarizing evidence that supports the relationship between cellular senescence and inflammation.
We then discuss the mechanisms of interaction between cellular senescence and inflammation, including senescence-associated secretory phenotypes (SASP) and the effects of pro- and anti-inflammatory interventions on cellular senescence. Additionally, we focus on various types of cellular senescence in OA, including senescence in cartilage, subchondral bone, synovium, infrapatellar fat pad, stem cells, and immune cells, elucidating their mechanisms and impacts on OA. Finally, we highlight the potential of therapies targeting senescent cells in OA as a strategy for promoting cartilage regeneration.