Tanaka Michiaki, Masuko-Hongo Kayo, Kato Tomohiro, Nishioka Kusuki, Nakamura Hiroshi
Department of Bioregulation, Institute of Medical Science, St. Marianna University School of Medicine, Sugao, Kawasaki, 216-8512, Japan.
Rheumatol Int. 2006 Jan;26(3):185-90. doi: 10.1007/s00296-004-0547-9. Epub 2004 Dec 3.
The purpose of the study was to examine the effects of hyaluronan (HA) on human chondrocytes in terms of production of MMP-1 and RANTES. Chondrocytes were obtained from patients with osteoarthritis (OA) or femoral neck fracture (control). Chondrocytes in monolayer culture were treated with various molecular weights (1.2, 50, 800 and 1,900 kD) of HA and then stimulated with IL-1beta. Production and expression of MMP-1 and RANTES were quantified by ELISA and real-time polymerase chain reaction (PCR). The response was blocked by anti-CD44 antibody. Production of MMP-1 was significantly suppressed by both 800- and 1,900-kD HA, while production of RANTES was suppressed by 1,900-kD HA. Expression of MMP-1 and RANTES mRNA was inhibited by 1,900-kD HA. Suppressive effects of HA on production of MMP-1 were canceled by treatment of anti-CD44 antibody. Higher CD44 expression was found in OA chondrocytes than in those of control. High-molecular-weight HA suppressed MMP-1 and RANTES production, mediated partly by CD44-HA interaction.
本研究的目的是从基质金属蛋白酶-1(MMP-1)和调节激活正常T细胞表达和分泌的趋化因子(RANTES)的产生方面,研究透明质酸(HA)对人软骨细胞的影响。软骨细胞取自骨关节炎(OA)患者或股骨颈骨折患者(对照组)。将单层培养的软骨细胞用不同分子量(1.2、50、800和1900 kD)的HA处理,然后用白细胞介素-1β(IL-1β)刺激。通过酶联免疫吸附测定(ELISA)和实时聚合酶链反应(PCR)对MMP-1和RANTES的产生及表达进行定量分析。该反应被抗CD44抗体阻断。800 kD和1900 kD的HA均显著抑制MMP-1的产生,而1900 kD的HA抑制RANTES的产生。1900 kD的HA抑制MMP-1和RANTES mRNA的表达。HA对MMP-1产生的抑制作用被抗CD44抗体处理所消除。OA软骨细胞中的CD44表达高于对照组。高分子量HA抑制MMP-1和RANTES的产生,部分由CD44-HA相互作用介导。