The DNA Repair Enzyme Apurinic/Apyrimidinic Endonuclease (Apex Nuclease) 2 Has the Potential to Protect against Down-Regulation of Chondrocyte Activity in Osteoarthritis

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

The NAD-Dependent Deacetylase Sirtuin-1 Regulates the Expression of Osteogenic Transcriptional Activator Runt-Related Transcription Factor 2 (Runx2) and Production of Matrix Metalloproteinase (MMP)-13 in Chondrocytes in Osteoarthritis

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

Long Term Changes in Muscles around the Knee Joint after ACL Resection in Rats: Comparisons of ACL-Resected, Contralateral and Normal Limb

The purpose of this study was to investigate the long-term effects of anterior cruciate ligament (ACL) resection on the morphological and contractile characteristics of rectus femoris (RF) and semimembranosus (SM) muscles in both injured and contralateral hindlimbs in rats. Wistar male rats (8-week old) were used. Rats were divided into two groups; ACL-resected and (sham-operated) control groups. Furthermore, right and left limbs of rats in the ACL-resected group were assigned as ACL-resected and contralateral groups, respectively, at 1 day, 1, 4, and 48 weeks after ACL resection. No ACL-resection-associated changes in the mass of both muscles were observed 1 week after ACL resection. On the other hand, ACL-resection-associated reduction on mean fiber cross-sectional area (fiber CSA) in RF muscle lasted 48 weeks after ACL resection. Furthermore, ACL-resection associated increase in fiber composition of type I fiber in RF muscle in contralateral limbs. In addition, long-term effects of ACL resection were observed in both ACL-resected and contralateral limbs. Evidences from this study suggested that ACL resection may cause to change in the morphological (fiber CSA) and contractile (distribution of fiber types) properties of skeletal muscles around the knee joint in not only injured but also contralateral limb. Rehabilitation for quantitative and qualitative muscle changes by ACL resection may be required a special care for a long-term period