Terada Chuji, Yoshida Aki, Nasu Yoshihisa, Mori Shuji, Tomono Yasuko, Tanaka Masato, Takahashi Hideo K, Nishibori Masahiro, Ozaki Toshifumi, Nishida Keiichiro
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Acta Med Okayama. 2011 Dec;65(6):369-77. doi: 10.18926/AMO/47262.
We investigated the expression and localization of high-mobility group box chromosomal protein-1 (HMGB-1) in human osteoarthritic (OA) cartilage in relation to the histopathological grade of cartilage destruction, and examined the role of HMGB-1 in the regulation of proinflammatory cytokine expression in chondrocytes. An immunohistochemical study demonstrated that total HMGB-1-positive cell ratios increase as the Osteoarthritis Research Society International (OARSI) histological grade increased. The population of cytoplasmic HMGB-1-positive chondrocytes was especially increased in the deep layers of higher-grade cartilage. The ratios and localization of receptors for advanced glycation end products (RAGE) expression by chondrocytes in Grade 2, 3, and 4 were significantly higher than those in Grade 1. In vitro stimulation with IL-1β, but not TNFα, significantly upregulated the expression of HMGB-1 mRNA by human OA chondrocytes. Both IL-1β and TNFα promoted the translocation of HMGB-1 from nuclei to cytoplasm. IL-1β and TNFα secretions were stimulated at higher levels of HMGB-1. The results of our study suggest the involvement of HMGB-1 in the pathogenesis of cartilage destruction in OA.
我们研究了高迁移率族蛋白B1（HMGB-1）在人类骨关节炎（OA）软骨中的表达和定位与软骨破坏组织病理学分级的关系，并探讨了HMGB-1在调节软骨细胞中促炎细胞因子表达方面的作用。一项免疫组织化学研究表明，随着国际骨关节炎研究学会（OARSI）组织学分级的增加，总HMGB-1阳性细胞比例升高。在高级别软骨深层，细胞质HMGB-1阳性软骨细胞的数量尤其增加。2级、3级和4级软骨细胞中晚期糖基化终产物受体（RAGE）表达的比例和定位显著高于1级。用IL-1β而非TNFα进行体外刺激可显著上调人OA软骨细胞中HMGB-1 mRNA的表达。IL-1β和TNFα均促进HMGB-1从细胞核向细胞质的转运。在较高水平的HMGB-1刺激下，IL-1β和TNFα的分泌增加。我们的研究结果提示HMGB-1参与了OA软骨破坏的发病机制。
