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The trial of treatment for temporomandibular joint osteoarthritis with soluble tumor necrosis factor receptor

可溶性肿瘤坏死因子受体治疗颞下颌关节骨关节炎的试验

基本信息

批准号：
15592050
负责人：
MAEKAWA Kenji
金额：
$ 2.18万
依托单位：
OKAYAMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

In this study, we tried to confirm soluble tumor necrosis factor receptor(sTNFR)-I,II concentrations in synovial fluids of osteoarthritic temporomandibular joint (OA) and to investigate the expression changes of sTNFR-I,II in the articular chondrocytes under an osteoarthritis-mimicking condition.1.sTNFR-I and -II concentrations were higher in the synovial fluids from OA patients than from asymptomatic controls.2.sTNFR-I concentration was higher than sTNFR-II concentration in the synovial fluids from both of patients and asymptomatic controls.3.sTNFR-I concentration in the synovial fluids was significantly related to the OA level.4.Higher sTNFR-II concentration in the synovial fluids was associated with less pain and less restricted range of mouth opening in the osteoarthritic patients.5.In the knee osteoarthritis rat model, both of TNFR-I and TNFR-II were found at the knee joint chondrocyte of arthritic side and control side, and in the arthritic side both of receptors were up-regulated.6.IL-1β and/or TNFα addition to the culture medium up-regulated tnfr-I,-II gene expression levels of the cultured chondrocytes and specifically sTNFR-II protein concentration in the cultured medium.Since IL-1β and/or TNFα addition to the culture medium up-regulated tnfr-II gene expression levels of the cultured chondrocytes and sTNFR-II protein concentration in the cultured medium, observed sTNFR-II up-regulation in the synovial fluids of the osteoarthritic patients could reflect the protective chondrocyte metabolism of the osteoarthritic joint. Even in the osteoarthritic joints, sTNFR-II could modulate inflammation and destruction of the temporomandibular articular tissues.Therefore, novel therapies may include agents that specifically mimic the anti-inflammatory feedback mechanism of sTNFR-II in vivo. We speculate that injection into temporomandibular joint with Etanercept, a potent inhibitor of TNFα, will be effective treatment for OA.

本研究通过检测颞下颌关节炎（OA）患者关节液中可溶性肿瘤坏死因子受体（sTNFR）-I、II的含量，探讨sTNFR-I、sTNFR-II在OA关节液中的表达变化，1. OA患者滑液中sTNFR-I和-II浓度高于无症状对照组关节滑液中sTNFR-I浓度与OA水平显著相关（P < 0. 05）。关节液中II浓度与骨关节炎患者疼痛减轻和张口受限范围减少相关。5.在膝关节在骨关节炎大鼠模型中，关节炎侧和对照侧的膝关节软骨细胞均存在TNFR-I和TNFR-II，并且关节炎侧的两种受体均上调。6.培养液中加入IL-1β和/或TNFα上调TNFR-I，由于IL-1β和/或sTNFR-II基因的表达水平以及培养液中sTNFR-II蛋白的浓度，或TNFα的加入上调了培养软骨细胞tnfr-II基因表达水平和培养液中sTNFR-II蛋白浓度，观察到骨关节炎患者滑液中sTNFR-II的上调可能反映了骨关节炎关节软骨细胞的保护性代谢。即使在骨关节炎关节中，sTNFR-II也可以调节颞下颌关节组织的炎症和破坏，因此，新的治疗方法可能包括特异性模拟sTNFR-II体内抗炎反馈机制的药物。我们推测，颞下颌关节内注射TNFα的有效抑制剂依那西普将是治疗OA的有效方法。