PINK1 overexpression suppresses p38 MAPK/NF‑κB signaling to attenuate chondrocyte senescence in osteoarthritis

PTEN‑induced putative kinase 1 (PINK1), a master regulator of mitophagy, is implicated in mitochondrial homeostasis, yet its role in knee osteoarthritis (OA) pathogenesis remains unclear. The present study investigated the mechanisms by which PINK1 modulates chondrocyte senescence during OA progression. Utilizing a destabilization of the medial meniscus‑induced OA murine model, decreased PINK1 expression, impaired mitochondrial function and suppressed mitophagy were observed in OA cartilage. <i>In vitro</i>, lipopolysaccharide‑induced chondrocyte senescence was exacerbated by PINK1 knockdown but mitigated by PINK1 overexpression, which restored mitophagy and reduced senescence‑associated β‑galactosidase activity, reactive oxygen species accumulation and mitochondrial membrane potential collapse. RNA sequencing and mechanistic studies identified the p38 MAPK/NF‑κB pathway as a downstream target; PINK1 knockdown amplified the phosphorylation of p38 MAPK/NF‑κB, promoting mitochondrial dysfunction and senescence. By contrast, pharmacological inhibition of p38 MAPK/NF‑κB rescued these effects in PINK1‑deficient chondrocytes. Collectively, PINK1 attenuated OA progression by suppressing chondrocyte senescence via inhibition of the p38 MAPK/NF‑κB pathway, highlighting its potential as a therapeutic target for OA management.