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破骨细胞相关受体 (OSCAR) 在活动期 RA 患者滑膜组织中的分布,以及破骨细胞体外对 TNF-α 和 RANKL 表达的调控。

Osteoclast-Associated Receptor (OSCAR) Distribution in the Synovial Tissues of Patients with Active RA and TNF-α and RANKL Regulation of Expression by Osteoclasts In Vitro.

机构信息

Discipline of Anatomy and Pathology, Adelaide Medical School, The University of Adelaide, Adelaide, 5005, Australia.

School of Population Health, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, 5005, Australia.

出版信息

Inflammation. 2017 Oct;40(5):1566-1575. doi: 10.1007/s10753-017-0597-2.

Abstract

Osteoclast-associated receptor (OSCAR) is a co-stimulatory receptor in osteoclastogenesis. Synovial tissues from active rheumatoid arthritis (RA) patients express higher levels of OSCAR compared with osteoarthritic and normal patients; however, the comparison of OSCAR levels in different regions of active RA synovium has not been reported. The regulation of OSCAR by TNF-α and receptor activator of NF kappa β ligand (RANKL) in pre-osteoclasts/osteoclasts in vitro is unclear. OSCAR and tartrate-resistant acid phosphatase (TRAP) expression levels did not differ between the cartilage pannus junction (CPJ) and non-CPJ regions in active RA. We demonstrate a similar pattern of OSCAR expression in the CPJ and non-CPJ synovial tissue from patients with active RA. OSCAR was associated with mononuclear cells in both the lining and sub-lining and endothelial cells (von Willebrand factor positive). Pre-osteoclasts (TRAP-positive cells) were present in the lining and sub-lining of both regions. OSCAR messenger RNA (mRNA) expression and release by pre-oscteoclasts/osteoclasts was modulated by RANKL with/without TNF-α in vitro. Osteoclast resorption on dentine slices was significantly greater with TNF-α pre-treatment and RANKL (10 ng/ml) than RANKL 10 or 50 ng/ml alone or RANKL 10 ng/ml with TNF-α given from day 3 post-RANKL. The lower levels of OSCAR mRNA expression corresponded with high osteoclast activity levels.

摘要

破骨细胞相关受体(OSCAR)是破骨细胞生成中的共刺激受体。与骨关节炎和正常患者相比,处于活动期类风湿关节炎(RA)患者的滑膜组织表达更高水平的 OSCAR;然而,尚未报道在活动期 RA 滑膜的不同区域比较 OSCAR 水平。TNF-α和核因子 κB 配体受体激活剂(RANKL)在体外破骨前体细胞/破骨细胞中对 OSCAR 的调节尚不清楚。在处于活动期的 RA 中,软骨滑膜交界(CPJ)和非 CPJ 区域的 OSCAR 和抗酒石酸酸性磷酸酶(TRAP)表达水平没有差异。我们在处于活动期的 RA 患者的 CPJ 和非 CPJ 滑膜组织中观察到类似的 OSCAR 表达模式。OSCAR 与衬里和衬里下层的单核细胞以及内皮细胞(血管性血友病因子阳性)相关。两个区域的衬里和衬里下层都存在破骨前体细胞(TRAP 阳性细胞)。体外 RANKL 可调节破骨前体细胞/破骨细胞的 OSCAR mRNA 表达和释放,无论是否存在 TNF-α。与 RANKL 10 或 50ng/ml 单独或 RANKL 10ng/ml 加 TNF-α在第 3 天给予相比,TNF-α预处理和 RANKL(10ng/ml)可显著增加牙本质切片上的破骨细胞吸收。OSCAR mRNA 表达水平较低与破骨细胞活性水平较高相对应。

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