NOS inhibition reverses TLR2-induced chondrocyte dysfunction and attenuates age-related osteoarthritis.

ABSTRACT: Osteoarthritis (OA) is a joint disease featuring cartilage breakdown and chronic pain. Although age and joint trauma are prominently associated with OA occurrence, the trigger and signaling pathways propagating their pathogenic aspects are ill defined. Following long-term catabolic activity and traumatic cartilage breakdown, debris accumulates and can trigger Toll-like receptors (TLRs). Here we show that TLR2 stimulation suppressed the expression of matrix proteins and induced an inflammatory phenotype in human chondrocytes. Further, TLR2 stimulation impaired chondrocyte mitochondrial function, resulting in severely reduced adenosine triphosphate (ATP) production. RNA-sequencing analysis revealed that TLR2 stimulation upregulated nitric oxide synthase 2 (NOS2) expression and downreg

SUBMITTER: Shen P 

PROVIDER: S-EPMC10629581 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature