Aging is one of the major pathologic factors associated with osteoarthritis (OA). Recently, numerous reports have demonstrated the impact of sirtuin-1 (Sirt1), which is the NAD-dependent deacetylase, on human aging. It has been demonstrated that Sirt1 induces osteogenic and chondrogenic differentiation of mesenchymal stem cells. However, the role of Sirt1 in the OA chondrocytes still remains unknown. We postulated that Sirt1 regulates a hypertrophic chondrocyte lineage and degeneration of articular cartilage through the activation of osteogenic transcriptional activator Runx2 and matrix metalloproteinase (MMP)-13 in OA chondrocytes. To verify whether sirtuin-1 (Sirt1) regulates chondrocyte activity in OA, we studied expressions of Sirt1, Runx2 and production of MMP-13, and their associations in human OA chondrocytes. The expression of Sirt1 was ubiquitously observed in osteoarthritic chondrocytes; in contrast, Runx2 expressed in the osteophyte region in patients with OA and OA model mice. OA relating catabolic factor IL-1βincreased the expression of Runx2 in OA chondrocytes. OA chondrocytes, which were pretreated with Sirt1 inhibitor, inhibited the IL-1β-induced expression of Runx2 compared to the control. Since the Runx2 is a promotor of MMP-13 expression, Sirt1 inactivation may inhibit the Runx2 expression and the resultant down-regulation of MMP-13 production in chondrocytes. Our findings suggest thatSirt1 may regulate the expression of Runx2, which is the osteogenic transcription factor, and the production of MMP-13 from chondrocytes in OA. Since Sirt1 activity is known to be affected by several stresses, including inflammation and oxidative stress, as well as aging, SIRT may be involved in the development of OA.

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.

Exercise increases oxidative stress, leading the body to strengthen its antioxidant defenses, thus reducing the incidence of major diseases. As these associations are relatively unclear for ordinary levels of exercise for reduced stress, this study evaluated the effects of different exercise conditions on diacron-reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), and subjective mood. Forty-nine students (22.4 ± 2.6 years) were assessed using the Profile of Mood States (POMS) before and after exercising for 60 min. Participants were divided into two groups: Group A engaged in compulsory sports and Group B in freely chosen sports. d-ROMs and BAP were measured, and their modified ratio was calculated as an index of antioxidant potential. Physiological evaluation showed significant improvements in BAP and the BAP/d-ROMs ratio, irrespective of exercise condition (p < 0.001, p < 0.01). Comparison between the exercise conditions revealed a significant difference in the modified ratio (p < 0.02). In mood assessment, scores on emotion-related scales without vigor improved significantly under both exercise conditions (p < 0.001). Mental changes were evident after exercise, and potential antioxidant capacity was higher in freely chosen sports (p < 0.03). Assessment of antioxidant status before and after exercise may provide an objective index of mental and physical conditioning.