Pterostilbene Improves Apoptosis, Inflammation, and Autophagy of Osteoarthritis Chondrocytes Through the Ras/Raf/MEK/ERK Pathway

The objective of this study was to investigate whether pterostilbene ameliorates chondrocyte injury in osteoarthritis by regulating the rat sarcoma virus/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathway. The animal model of osteoarthritis was established, and interleukin-1β-treated chondrocytes were cultured. In vivo and in vitro models were treated with different doses of pterostilbene. Hematoxylin-eosin staining and safranin O-fast green staining were used to evaluate the pathological injury degree of cartilage tissue. Chondrocyte viability was assessed by cell counting kit-8 assay, apoptosis was detected by flow cytometry, and autophagosomes were measured by monodansylcadaverine staining. Enzyme-linked immunosorbent assay measured tumor necrosis factor-α, interleukin-1β, and interleukin-6 in cartilage tissue and chondrocytes. Western blot or real-time reverse transcriptase-polymerase chain reaction was conducted to detect matrix metalloproteinase-1, matrix metalloproteinase-13, cleaved caspase-3, phosphorylated p65, p65, p62, autophagy-related gene 5, phosphorylated extracellular signal-regulated kinase, and phosphorylated mitogen-activated protein kinase kinase in chondrocytes and tissues. Pterostilbene attenuated articular cartilage injury, repaired cartilage tissue morphology, and suppressed inflammatory factors in osteoarthritis mice. Pterostilbene reduced interleukin-1β-induced chondrocyte injury, increased cell viability, reduced apoptosis rate, promoted autophagosome formation, and inhibited levels of chondrocyte inflammatory factors. In osteoarthritis mice and interleukin-1β-treated chondrocytes, pterostilbene inhibited matrix metalloproteinase-1, matrix metalloproteinase-13, cleaved caspase-3, phosphorylated p65, and p62 expressions, and promoted autophagy-related gene 5 expression. Pterostilbene blocked rat sarcoma virus/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathway activation. Pterostilbene and extracellular signal-regulated kinase inhibitors had a synergistic effect in the treatment of chondrocyte injury, and extracellular signal-regulated kinase agonists reversed the therapeutic effect of pterostilbene. Pterostilbene improves chondrocyte injury by blocking rat sarcoma virus/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathway activation.