Adiponectin aggravates bone erosion by promoting osteopontin production in synovial tissue of rheumatoid arthritis.
Adiponectin aggravates bone erosion by promoting osteopontin production in synovial tissue of rheumatoid arthritis.
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脂联素通过促进类风湿性关节炎滑膜组织中骨桥蛋白的产生而加重骨侵蚀
DOI：
10.1186/s13075-018-1526-y
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发表时间：
2018-02-08
影响因子：
4.9
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
Qian J;Xu L;Sun X;Wang Y;Xuan W;Zhang Q;Zhao P;Wu Q;Liu R;Che N;Wang F;Tan W;Zhang M
研究背景脂联素（adiponectin，AD）是一种由脂肪细胞分泌的脂肪因子，与类风湿关节炎（rheumatoid arthritis，RA）的骨侵蚀密切相关。AD促进关节破坏的确切机制尚不清楚。骨桥蛋白（OPN）是破骨细胞募集所必需的。我们假设AD通过诱导滑膜组织中OPN的表达而加重骨侵蚀。本研究旨在评估AD在RA中的新作用。方法采用酶联免疫吸附试验（ELISA）检测38例RA患者、40例骨关节炎（OA）患者和20例健康对照者血清AD和OPN水平。用免疫荧光双标法检测RA和OA滑膜组织中AD和OPN的表达。采用实时定量PCR和免疫荧光技术分别检测AD预孵育后RA滑膜成纤维细胞（RASFs）和OA滑膜成纤维细胞中OPN的mRNA和蛋白表达水平。使用Transwell迁移测定和共培养系统评估RAW 264.7破骨细胞前体细胞系的迁移。通过免疫组织化学染色、显微计算机断层扫描和抗酒石酸酸性磷酸酶（TRAP）染色，在有或没有OPN沉默的AD治疗的胶原诱导的关节炎（CIA）小鼠中评估骨破坏和破骨细胞生成。结果RA血清中AD和OPN的表达水平明显升高，且两者之间存在相关性。AD与OPN在RA滑膜组织中的分布一致。AD刺激RASFs以剂量依赖性方式增加OPN的产生。AD处理的RASFs促进RAW264.7细胞迁移，并且该作用被针对OPN的特异性抗体阻断。使用慢病毒-OPN短发夹RNA沉默OPN减少了AD治疗的CIA小鼠中TRAP阳性破骨细胞的数量和骨质侵蚀的程度。当与整合素αvβ3结合时，OPN作为AD和破骨细胞的介导者发挥作用。AD诱导OPN的表达，OPN募集破骨细胞并启动骨侵蚀。这些数据突出了AD作为RA治疗的新靶点。
BackgroundWe have previously reported that adiponectin (AD), an adipokine that is secreted by adipocytes, correlates well with progressive bone erosion in rheumatoid arthritis (RA). The exact mechanism of AD in promoting joint destruction remains unclear. Osteopontin (OPN) is required for osteoclast recruitment. We hypothesized that AD exacerbates bone erosion by inducing OPN expression in synovial tissue. This study aimed to evaluate a novel role for AD in RA.MethodsThe serum levels of AD and OPN were determined in 38 patients with RA, 40 patients with osteoarthritis (OA), and 20 healthy controls using enzyme-linked immunosorbent assay (ELISA). AD and OPN production were measured by double immunofluorescence in RA and OA synovial tissue. Quantitative real-time PCR and immunofluorescence were used to evaluate the mRNA and protein expression levels of OPN in RA synovial fibroblasts (RASFs) and OA synovial fibroblasts after pre-incubation with AD, respectively. Migration of the RAW264.7 osteoclast precursor cell line was assessed using the Transwell migration assay and co-culture system. Bone destruction and osteoclastogenesis were assessed by immunohistochemical staining, microcomputed tomography and tartrate-resistant acid phosphatase (TRAP) staining in AD-treated collagen-induced arthritis (CIA) mice with or without OPN silencing. The expression levels of OPN and integrin αvβ3in the ankle joint tissues of the mice were examined by double immunofluorescence.ResultsOur results indicated that the AD and OPN expression levels increased noticeably and were associated with each other in the RA serum. The AD distribution was coincident with that of OPN in the RA synovial tissue. AD stimulation of RASFs increased OPN production in a dose-dependent manner. AD-treated RASFs promoted RAW264.7 cell migration, and the effect was blocked with a specific antibody against OPN. Silencing of OPN using lentiviral-OPN short hairpin RNA reduced the number of TRAP-positive osteoclasts and the extent of bone erosion in the AD-treated CIA mice. When bound to integrin αvβ3, OPN functions as a mediator of AD and osteoclasts.ConclusionsOur study provides new evidence of AD involvement in bone erosion. AD induces the expression of OPN, which recruits osteoclasts and initiates bone erosion. These data highlight AD as a novel target for RA treatment.
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脂联素通过增强 Th17 反应和促进 RANKL 表达加剧胶原诱导的关节炎
影响因子：
4.6
作者：
Sun X;Feng X;Tan W;Lin N;Hua M;Wei Y;Wang F;Li N;Zhang M
通讯作者：
Zhang M
影响因子：
2.5
作者：
Iwadate, Haruyo;Kobayashi, Hiroko;Ohira, Hiromasa
通讯作者：
Ohira, Hiromasa
DOI：
10.1038/nrrheum.2012.153
发表时间：
2012-11
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
29
作者：
Stern JH;Rutkowski JM;Scherer PE
通讯作者：
Scherer PE
DOI：
10.1016/j.bbrc.2004.02.124
发表时间：
2004-04-09
影响因子：
3.1
作者：
Ishii, T;Ohshima, S;Saeki, Y
通讯作者：
Saeki, Y