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Analysis of inhibitory mechanisms of synovial proliferation with vitamin D3

维生素D3抑制滑膜增殖的机制分析

基本信息

批准号：
06670505
负责人：
HIGAKI Megumu
金额：
$ 1.34万
依托单位：
St.Marianna Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670505/
关键词：
Vitamin D3 Rheumatoid arthritis Synovial cells cytokine proliferation transcription factor cell cycle cyclin 細胞増殖コラゲナーゼ

项目摘要

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized with neocvascularization, lymphocytes infiltration and lining cell hyperplasia in inflamed synovial tissues. The hyperproliferated synovial cells called pannus consists of macrophage-like type A synoviocytes and fibroblast-like type B synoviocytes. The type B synoviocytes, which are activated with cytokines such as IL-1 and PDGF produced by type A synoviocytes, proliferate and produce many chemical mediators including cytokines, MMPs, and PGs. Here we have examined the inhibitory effect of vitamin D3 against the activation and proliferation of type B synoviocytes. Vitamin D3, but not dexamethasone, inhibited the proliferation of synoviocytes from RA and osteoarthritis patients dose-dependently. Vitamin D3 inhibited the growth of synoviocytes in G1 phase in cell-cyle analysis using flow cytometry and the inhibition of the expression of cyclin D1 was shown in northern blot analysis. Vitamin D3 also suppressed the production of IL-6 and collagenase, but not TIMP from synoviocytes. Gelatin zymograph also showded the reduction of collagenase acitivity with vitamin D3. And gel-shift assay revealed that vitamin D3 as well as dexamethasone inhibited the nuclear factor AP-1 of IL-1 stimulated synoviocytes.It is Shown that vitamin D3 inhibited the activation and proliferation of type B synoviocytes and might modulate the pathology of RA.

类风湿性关节炎（RA）是一种以炎症性滑膜组织新生血管、淋巴细胞浸润和衬里细胞增生为特征的慢性炎症性疾病。过度增殖的滑膜细胞称为血管翳，由巨噬细胞样A型滑膜细胞和成纤维细胞样B型滑膜细胞组成。B型滑膜细胞被A型滑膜细胞产生的细胞因子如IL-1和PDGF激活，增殖并产生许多化学介质，包括细胞因子、MMP和PG。在这里，我们研究了维生素D3对B型滑膜细胞的激活和增殖的抑制作用。维生素D3，而不是地塞米松，抑制RA和骨关节炎患者滑膜细胞的增殖呈剂量依赖性。流式细胞仪分析显示维生素D3可抑制滑膜细胞生长于G1期，北方印迹分析显示维生素D3可抑制细胞周期蛋白D1的表达。维生素D3还抑制IL-6和胶原酶的产生，但不抑制滑膜细胞的TIMP。明胶酶谱也显示维生素D3降低胶原酶活性。凝胶迁移实验表明，维生素D3和地塞米松对IL-1刺激的滑膜细胞核因子AP-1有抑制作用，提示维生素D3可抑制B型滑膜细胞的活化和增殖，可能参与RA的病理过程。