Chondrocyte apoptosis is a central feature in the progression of osteoarthritis (OA), and would be triggered by sustained elevation of intracellular calcium ion (Ca2+), also known as a cellular second messenger. Transient receptor potential ankyrin 1 (TRPA1) is a membrane-associated cation channel, and the activation of which causes an influx of cation ions, in particularly Ca2+, into the activated cells. Therefore, we investigate the potential role of TRPA1 in mediating Ca2+ influx to promote chondrocyte apoptosis in OA. The expression of TRPA1 in interleukin (IL)-1β-treated rat chondrocytes was assessed by Polymerase chain reaction (PCR) and Western blot (WB), and the functionality of TRPA1 channel by Ca2+ influx measurements. Meanwhile, the chondrocyte apoptosis in IL-1β-treated cells was measured by TUNEL assay and flow cytometry. The measurement of mitochondrial membrane potential and apoptosis-associated proteins after inhibition of TRPA1 were also performed in IL-1β-treated rat chondrocytes. After being induced by IL-1β, the gene and protein expression of TRPA1 was increased in the dose-dependent manner. Meanwhile, Ca2+ influx mediated by TRPA1 in rat chondrocytes was also enhanced. Pharmacological inhibition of TRPA1 downregulated the apoptotic rate in IL-1β-treated rat chondrocytes. In addition, the membrane potential depolarization was improved and significantly increased expression of apoptosis-associated proteins also reduced by the TRPA1 antagonist. We found the IL-1β caused the increased functional expression of TRPA1, the activation of which involved IL-1β-induced apoptosis in rat chondrocytes. The potential mechanism may be linked to the intracellular calcium overload mediated by TRPA1 and attendant mitochondrial dysfunction.

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. In vitro, 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.