类风湿性病变中的维生素D受体:软骨细胞、巨噬细胞和滑膜细胞的表达
Vitamin D receptors in the rheumatoid lesion: expression by chondrocytes, macrophages, and synoviocytes.
作者信息
Tetlow L C, Smith S J, Mawer E B, Woolley D E
机构信息
University Department of Medicine, Manchester Royal Infirmary.
出版信息
Ann Rheum Dis. 1999 Feb;58(2):118-21. doi: 10.1136/ard.58.2.118.
OBJECTIVES
The active form of vitamin D3, 1 alpha,25 dihydroxyvitamin D3 (1,25D3), through its interaction with vitamin D receptors (VDR), is reported to effect a variety of anabolic and catabolic events, especially in bone and cartilage tissues. As cartilage degradation and tissue remodelling are characteristic features of the rheumatoid lesion, the distribution and expression of VDR at sites of cartilage erosion was examined.
METHODS
Immunolocalisation techniques using a rat monoclonal antibody to VDR and an alkaline phosphatase conjugated avidin/biotin detection system were used to examine VDR in 18 specimens of cartilage-pannus junction, 10 specimens of rheumatoid synovium or cartilage tissue, and four primary cultures of adherent rheumatoid synovial cells (RSC). For comparison, VDR expression was examined in 10 specimens of normal, healthy age matched articular cartilage.
RESULTS
VDR was demonstrated in 15 of 18 cartilage-pannus junctions either at the interface (8 of 18), within the pannus tissue (12 of 18), and by chondrocytes often close to the erosive lesion (10 of 18). All the rheumatoid synovial tissue and 5 of 10 cartilage specimens showed cells with positive staining, but the extent of this was variable. Negligible VDR staining was observed for normal cartilage. Primary cultures of RSC also showed variability in both the numbers and proportions of macrophages or synovial fibroblasts stained for VDR (range 10-50%), this being more common in cultures with a high proportion of macrophages.
CONCLUSIONS
VDR expression has been demonstrated by most specimens of cartilage-pannus junction; was associated with various cell types, including chondrocytes, but not exclusively with CD68+ macrophages. The focal nature of VDR expression within the rheumatoid lesion suggests a contributory role for 1 alpha,25D3 in the pathophysiological processes of rheumatoid arthritis.
目的
据报道,维生素D3的活性形式1α,25-二羟基维生素D3(1,25D3)通过与维生素D受体(VDR)相互作用,可影响多种合成代谢和分解代谢过程,尤其是在骨骼和软骨组织中。由于软骨降解和组织重塑是类风湿性病变的特征性表现,因此研究了VDR在软骨侵蚀部位的分布和表达情况。
方法
采用针对VDR的大鼠单克隆抗体和碱性磷酸酶偶联抗生物素蛋白/生物素检测系统的免疫定位技术,检测18个软骨-血管翳交界处标本、10个类风湿性滑膜或软骨组织标本以及4个贴壁类风湿性滑膜细胞(RSC)原代培养物中的VDR。作为对照,检测了10个正常、健康且年龄匹配的关节软骨标本中的VDR表达。
结果
在18个软骨-血管翳交界处的15个标本中检测到VDR,其中在界面处(18个中有8个)、血管翳组织内(18个中有12个)以及常靠近侵蚀性病变的软骨细胞中(18个中有10个)均可检测到。所有类风湿性滑膜组织以及10个软骨标本中的5个显示细胞呈阳性染色,但染色程度各不相同。正常软骨中观察到的VDR染色可忽略不计。RSC原代培养物中,VDR染色的巨噬细胞或滑膜成纤维细胞数量和比例也存在差异(范围为10%-50%),在巨噬细胞比例较高的培养物中更为常见。
结论
大多数软骨-血管翳交界处标本均显示有VDR表达;VDR与多种细胞类型相关,包括软骨细胞,但并非仅与CD68+巨噬细胞相关。类风湿性病变中VDR表达的局灶性表明1α,25D3在类风湿性关节炎的病理生理过程中起一定作用。