Emerging Players at the Intersection of Chondrocyte Loss of Maturational Arrest, Oxidative Stress, Senescence and Low-Grade Inflammation in Osteoarthritis.

摘要: The prevalence of Osteoarthritis (OA) is increasing because the progressive aging and unhealthy lifestyle. These risk factors trigger OA by removing constraints that keep tightly regulated low turnover extracellular matrix (ECM) articular cartilage, correct chondrocyte phenotype, functionality major homeostatic mechanisms, such as mitophagy, allows for clearance dysfunctional mitochondria, preventing increased production reactive oxygen species, oxidative stress, senescence. After onset, presence ECM degradation products perceived a “danger” signal chondrocytes synovial macrophages release alarmins with autocrine/paracrine effects on same cells. Alarmins innate immunity in joint, important systemic crosstalks explain beneficial dietary interventions improved also boost low-grade inflammation: inflammatory molecules chemokines sustained continuous triggering NF-κB within an altered cellular setting its higher transcriptional activity. Chemokines exert pleiotropic functions OA, including recruitment cells induction remodeling. Some have been successfully targeted to attenuate structural damage or pain animal models. This represents promising strategy future management human OA.