Osteoarthritis (OA) is one of the most common types of arthritis in the elderly people. It has been known that chondrocyte apoptosis occurs in OA cartilage; however, the detailed molecular mechanism remains unclear. In the current study, we aimed to elucidate the role of double-stranded RNA-dependent protein kinase R (PKR) in the TNF-α-caused apoptosis in chondrocytes. Human articular chondrocytes were digested from cartilages of OA subjects who accepted arthroplastic knee surgery. Our results showed that phosphorylation of p38 MAPK was increased after TNF-α stimulation or PKR activation using poly (I:C), and TNF-α-induced p38 MAPK upregulation was inhibited by PKR inhibition, suggesting phosphor-p38 MAPK was regulated by PKR. Moreover, we found that PKR participated in the p53-dependent destruction of AKT following activation of p38 MAPK. The inhibition of AKT led to the reduced expression of PGC-1α, which resulted in mitochondrial dysfunction and increased oxidative stress. We showed that the reduction of oxidative stress using antioxidant Mito TEMPO lowered the TNF-α-induced caspase-3 activation and TUNEL-positive apoptotic cells. The diminished apoptotic response was also observed after repression of PKR/p38 MAPK/p53/AKT/PGC-1α signaling. Taken together, we demonstrated that the aberrant mitochondrial biogenesis and increased oxidative stress in chondrocytes after TNF-α stimulation were mediated by PKR, which may contribute to the chondrocyte apoptosis and cartilage degeneration in OA.

and MMP-9 activities from its lowest concentration, and MMP-1 and MMP-2 at its higher concentrations, which implies a greater protective effect on elastin. It dramatically increased the expression of types I, III, and V collagens, and elastin, fibrillin-1, and fibrillin-2 in dermal fibroblasts. The effects were similar to those of ascorbic acid. This is the first report identifying xanthohumol's potential to improve skin structure and firmness: it simultaneously inhibits the activities of elastase/MMPs and stimulates the biosynthesis of fibrillar collagens, elastin, and fibrillins.pp. 133-145 Comparison of hydration, tyrosinase resistance, and antioxidant activation in three kinds of pearl powders by

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