Tetramethylpyrazine alleviates endoplasmic reticulum stress-activated apoptosis and related inflammation in chondrocytes

Excessive apoptosis of chondrocytes and degradation of the extracellular matrix (ECM) contribute to the typical pathological characteristics of osteoarthritis (OA). Various studies have reported that tetramethylpyrazine (TMP) protects against multiple disorders by inhibiting inflammation and oxidative stress. The present study investigated the effects of TMP on chondrocytes and evaluated the associated mechanisms. To determine the effect of TMP on OA and the underlying mechanisms, chondrocytes were incubated with TMP and IL-1 beta or thapsigargin (TG) Western blotting assays were performed to examine the expression levels of endoplasmic reticulum (ER) stress proteins, and TUNEL staining, fluorescence immunostaining and reverse transcription-quantitative PCR were used to determine the apoptosis levels, and catabolic and inflammatory factors. It was found that TMP protected chondrocytes by suppressing IL-1 beta-induced expression of glucose-regulated protein 78 (GRP78) and CHOP (an apoptotic protein). TMP regulated the TG-mediated upregulated expression of GRP78 and CHOP in the chondrocytes of rats, as well as markedly suppressed levels of ER stress-triggered inflammatory cytokines (TNF-alpha and IL-6). Furthermore, TMP modulated TG-induced changes in ECM catabolic metabolism in rat chondrocytes. Collectively, TMP alleviated ER-stress-activated apoptosis and related inflammation in chondrocytes, indicating that it has therapeutic potential for the treatment of OA.