Institute of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
Department of Pathology, Shandong University Medical School, Jinan, China.
Ann Rheum Dis. 2019 Dec;78(12):1632-1641. doi: 10.1136/annrheumdis-2019-215473. Epub 2019 Aug 27.
The aim of this study was to investigate the role of CD109 in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) and to evaluate its potential as a therapeutic target.
CD109 expression was examined in synovial tissues and FLSs from RA patients and collagen-induced arthritis (CIA) model mice. CD109-deficient mice were developed to evaluate the severity of CIA. Small interfering RNAs and a neutralising antibody against CD109 (anti-CD109) were designed for functional or treatment studies in RA FLSs and CIA.
CD109 was found to be abundantly expressed in the synovial tissues from RA patients and CIA mice. CD109 expression in RA FLSs was upregulated by inflammatory stimuli, such as interleukin-1β and tumour necrosis factor-α. Silencing of CD109 or anti-CD109 treatment reduced proinflammatory factor production, cell migration, invasion, chemoattractive potential and osteoclast differentiation, thereby reducing the deleterious inflammatory response of RA FLSs in vitro. Mice lacking CD109 were protected against arthritis in the CIA model. Anti-CD109 treatment prevented the onset and ameliorated the severity of CIA lesions.
Our study uncovers an antiarthritic role for CD109 and suggests that CD109 inhibition might serve as a promising novel therapeutic strategy for RA.
本研究旨在探讨 CD109 在类风湿关节炎（RA）成纤维样滑膜细胞（FLSs）中的作用，并评估其作为治疗靶点的潜力。
检测 RA 患者滑膜组织和胶原诱导性关节炎（CIA）模型小鼠的 FLSs 中 CD109 的表达。构建 CD109 缺陷型小鼠以评估 CIA 的严重程度。设计针对 RA FLSs 和 CIA 的小干扰 RNA（siRNA）和 CD109 中和抗体（抗 CD109）用于功能或治疗研究。
CD109 在 RA 患者和 CIA 小鼠的滑膜组织中大量表达。炎症刺激物，如白细胞介素-1β和肿瘤坏死因子-α，可上调 RA FLSs 中 CD109 的表达。沉默 CD109 或抗 CD109 治疗可减少促炎因子的产生、细胞迁移、侵袭、趋化作用和破骨细胞分化，从而减轻 RA FLSs 的有害炎症反应。缺乏 CD109 的小鼠可预防 CIA 模型中的关节炎。抗 CD109 治疗可预防 CIA 的发病并改善其严重程度。
本研究揭示了 CD109 的抗关节炎作用，并表明 CD109 抑制可能成为 RA 的一种有前途的新型治疗策略。
