The efficacy of rhTNFR:Fc and its effect on osteopontin in the collagen-induced arthritis mice model
10.3760/cma.j.issn.1007-7480.2011.01.005
- VernacularTitle:重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白在胶原诱导性关节炎大鼠中的疗效观察及其对骨桥蛋白的影响
- Author:
Zhifen LV
;
Yi TAO
;
Ruilin CHEN
;
Wenhui HUANG
- Publication Type:Journal Article
- Keywords:
Arthritis,experimental;
Synovial membrane;
Cartilage,articular;
Tumor necrosis factor-alpha;
rhTNFR;
Fc;
Osteopontin
- From:
Chinese Journal of Rheumatology
2011;15(1):17-21,后插2
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the protection effects of recombinant human tumor necrosis factor-α receptor Ⅱ :IgG Fc fusion protein for injection (rhTNFR:Fc) on rats with collagen-induced arthritis (CIA) and analyze osteopontin (OPN) changes following therapy in order to understand its primary mechanism of action. Methods CIA was induced by bovine Ⅱ collagen (B Ⅱ C) injection. Rats were treated with rhTNFR:Fc from the 13th day after the first injection of B Ⅱ C till the 36th day. The anterior-posterior diameters of ankle joints and weight were measured weekly. The pathological score was evaluated by HE staining and toluidine blue staining. The blood plasma TNF-α and OPN levels were measured by ELISA and the histology expression was evaluated by immuno-histochemistry. Comparisons between groups were performed with one-way ANOVA. Results Quantitative analysis showed pathological score in the model group and treatment group was significantly reduced in joint pathology (8.2±1.0 vs 4.8±1.4, P<0.05). The mean plasma levels of TNF-α and OPN values were (713±146) pg/ml, (4.3±0.6) ng/ml respectively in the model group,but those of the treatment group were (68±20) pg/ml, (4.2±0.6) ng/ml. Serum TNF-α values were significantly different (P<0.05) between the two groups, while no significant difference was found in the value of plasma OPN (P=0.688) between the two groups. rhTNFR:Fc could reduce the cells OPN expression in the interface layer of the synovium and cartilage (P<0.05). Conclusion Pathology scores and ELISA results haveshown that rhTNFR:Fc has good therapeutic efficacy. It can significantly reduce the bone and cartilage damage of CIA mouse model, and can significantly reduce the expression of OPN in the sliding joints, thereby delay disease progression. However, it can not reduce the expression of OPN in the peripheral blood plasma.OPN may be involved in bone destruction and resorption rather than in inflammatory process.
