Sakao Kei, Takahashi Kenji A, Arai Yuji, Saito Masazumi, Honjo Kuniaki, Hiraoka Nobuyuki, Asada Hidetsugu, Shin-Ya Masaharu, Imanishi Jiro, Mazda Osam, Kubo Toshikazu
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
J Bone Miner Metab. 2009;27(4):412-23. doi: 10.1007/s00774-009-0058-6. Epub 2009 Apr 1.
To clarify the significance of the osteophytes that appear during the progression of osteoarthritis (OA), we investigated the expression of inflammatory cytokines and proteases in osteoblasts from osteophytes. We also examined the influence of mechanical stress loading on osteoblasts on the expression of inflammatory cytokines and proteases. Osteoblasts were isolated from osteophytes in 19 patients diagnosed with knee OA and from subchondral bone in 4 patients diagnosed with femoral neck fracture. Messenger RNA expression and protein production of inflammatory cytokines and proteases were analyzed using real-time RT-PCR and ELISA, respectively. To examine the effects of mechanical loading, continuous hydrostatic pressure was applied to the osteoblasts. We determined the mRNA expression and protein production of IL-6, IL-8, and MMP-13, which are involved in the progression of OA, were increased in the osteophytes. Additionally, when OA pathological conditions were simulated by applying a nonphysiological mechanical stress load, the gene expression of IL-6 and IL-8 increased. Our results suggested that nonphysiological mechanical stress may induce the expression of biological factors in the osteophytes and is involved in OA progression. By controlling the expression of these genes in the osteophytes, the progression of cartilage degeneration in OA may be reduced, suggesting a new treatment strategy for OA.
为了阐明骨关节炎(OA)进展过程中出现的骨赘的意义,我们研究了骨赘中成骨细胞中炎性细胞因子和蛋白酶的表达。我们还研究了机械应力加载对成骨细胞中炎性细胞因子和蛋白酶表达的影响。从19例诊断为膝关节OA患者的骨赘以及4例诊断为股骨颈骨折患者的软骨下骨中分离出成骨细胞。分别使用实时逆转录聚合酶链反应(RT-PCR)和酶联免疫吸附测定(ELISA)分析炎性细胞因子和蛋白酶的信使核糖核酸(mRNA)表达及蛋白质生成情况。为了研究机械加载的影响,对成骨细胞施加持续静水压力。我们测定了参与OA进展的白细胞介素-6(IL-6)、白细胞介素-8(IL-8)和基质金属蛋白酶-13(MMP-13)的mRNA表达及蛋白质生成在骨赘中均增加。此外,当通过施加非生理性机械应力负荷模拟OA病理状况时,IL-6和IL-8的基因表达增加。我们的结果表明,非生理性机械应力可能诱导骨赘中生物因子的表达并参与OA进展。通过控制骨赘中这些基因的表达,OA中软骨退变的进展可能会减缓,这提示了一种新的OA治疗策略。