Figure 2. Senescent cells develop a SASP.

The nature of the SASP depends on the local microenvironment and will itself alter the local environment. The innate and adaptive immune system can respond to joint trauma and tissue injury. The SASP includes cytokines that attract and modulate immune cells, which remove debris and secrete cytokines that influence the tissue response toward repair or fibrosis. Elements of the immune system are also responsible for clearing SnCs that form after injury. When persistent, the molecules secreted by both SnCs and immune cells cause chronic inflammation and ultimately chronic disease. Three strategies (green text) potentially prevent or attenuate OA diseases by selectively eliminating SnCs: augmentation of immune-mediated SnC clearance (e.g., chimeric antigen receptor [CAR] T cells, which are engineered to express immunoglobulin variable fragments to SnC surface markers), SASP neutralization, and direct killing of SnCs by senolytics.