Yui Naoko, Yoshioka Hirotaka, Fujiya Hiroto, Musha Haruki, Beppu Moroe, Karasawa Rie, Yudoh Kazuo
Department of Sports Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan.
Department of Orthopedic Surgery, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan.
Int J Mol Sci. 2014 Aug 25;15(9):14921-34. doi: 10.3390/ijms150914921.
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.
脱嘌呤/脱嘧啶内切核酸酶2（Apex 2）在多种人类体细胞中由氧化损伤引起的DNA修复过程中发挥关键作用。我们推测软骨细胞中的Apex 2可能对骨关节炎（OA）中关节软骨的分解代谢过程起到保护作用。在STR/OrtCrlj小鼠（一种自发发展为OA的实验模型）中，与轻度退变的OA软骨相比，在重度退变的OA软骨中组织学观察到更高水平的Apex 2表达。Apex 2的免疫阳性与软骨退变程度显著相关。此外，OA相关的分解代谢因子白细胞介素-1β可诱导软骨细胞中Apex 2的表达，而使用小干扰RNA使Apex 2沉默则会降低体外软骨细胞的活性。因此，软骨细胞中Apex 2的表达似乎与关节软骨退变相关，并且可能由OA相关的分解代谢因子诱导，以保护关节软骨免受分解代谢过程的影响。我们的研究结果表明，Apex 2可能具有预防OA中分解代谢应激介导的软骨细胞活性下调的潜力。
