Abstract
Apurinic/apyrimidinic endonuclease 2 (Apex 2) plays a critical role in DNA repair caused by oxidative damage in a variety of human somatic cells. We speculated that chondrocyte Apex 2 may protect against the catabolic process of articular cartilage in osteoarthritis (OA). Higher levels of Apex 2 expression were histologically observed in severely compared with mildly degenerated OA cartilage from STR/OrtCrlj mice, an experimental model which spontaneously develops OA. The immunopositivity of Apex 2 was significantly correlated with the degree of cartilage degeneration. Moreover, the OA-related catabolic factor interleukin-1β induced the expression of Apex 2 in chondrocytes, while Apex 2 silencing using small interfering RNA reduced chondrocyte activity in vitro. The expression of Apex 2 in chondrocytes therefore appears to be associated with the degeneration of articular cartilage and could be induced by an OA-related catabolic factor to protect against the catabolic process of articular cartilage. Our findings suggest that Apex 2 may have the potential to prevent the catabolic stress-mediated down-regulation of chondrocyte activity in OA.
Highlights
Osteoarthritis (OA) symptoms and joint destruction become aggravated both as the disease advances and with aging, because damage progresses over time and articular cartilage has a reduced capacity for self-repair
OA chondrocytes spontaneously expressed higher levels of apyrimidinic endonuclease 2 (Apex 2) protein (Figure 3B). In those OA chondrocytes treated with IL-1β, the expression of Apex 2 protein temporarily decreased during the first 2 h of incubation but gradually increased and recovered (Figure 3C). These findings suggest that the expression of Apex 2 in chondrocytes is involved in the pathogenesis of OA
Because proteoglycan is a major component of articular cartilage, our results indicate the importance of Apex 2 in chondrocyte activity and the maintenance of articular cartilage
Summary
Osteoarthritis (OA) symptoms and joint destruction become aggravated both as the disease advances and with aging, because damage progresses over time and articular cartilage has a reduced capacity for self-repair. Numerous reports have demonstrated that chondrocytes produce excess amounts of reactive oxygen species (ROS) in the form of superoxide, nitric oxide, hydrogen peroxide, and peroxynitrite [1,2,3,4], as well as proinflammatory cytokines and chemokines in response to the mechanical forces imposed on articular cartilage [5,6,7]. This results in the depolymerization of hyaluronic acid and chondrocyte death in OA. Our current study suggests a novel mechanism for oxidative stress-mediated DNA damage in OA
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