Adenosine A2A Receptor Mediates Inhibition of Synovitis and Osteoclastogenesis after Electroacupuncture in Rats with Collagen-Induced Arthritis
Adenosine A2A Receptor Mediates Inhibition of Synovitis and Osteoclastogenesis after Electroacupuncture in Rats with Collagen-Induced Arthritis
复制标题
腺苷 A2A 受体介导胶原性关节炎大鼠电针后滑膜炎和破骨细胞生成的抑制
DOI：
10.1155/2019/4617464
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发表时间：
2019-01-01
影响因子：
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通讯作者：
Ye, Tian-shen
中科院分区：
文献类型：
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作者：
Du, Zhong-heng;Zhang, Chun-wu;Ye, Tian-shen
背景：本研究旨在探讨腺苷A2a受体(A2AR)在抑制电针(EA)对胶原诱导性关节炎(CIA)破骨细胞形成的影响中的作用。方法Wistar大鼠随机分为4组：假对照组、CIA对照组、CIA-EA组和CIA-EA-SCH58261(A2AR拮抗剂)组。采用酶联免疫吸附试验检测外周血中肿瘤坏死因子-α、核转录因子-αB、核转录因子-κB、受体激活剂核因子-κB配体、蛋白激酶A和细胞外调节蛋白激酶1/2(ERK1/2)。免疫印迹法检测踝关节组织中PKA、ERK1/2和NF-κB的表达。通过组织学检查评价关节炎损伤程度，用抗酒石酸酸性磷酸酶(TRAP)染色检测破骨细胞数。结果电针治疗可降低外周血中肿瘤坏死因子α、RANK1、PKA、ERK1/2和NF-κB的表达，升高踝关节中PKA和ERK1/2的水平。重要的是，电针治疗减少了骨侵蚀的组织学发现和抑制破骨细胞的形成，如TRAP染色揭示。电针与A2AR拮抗剂SCH58261联合应用，可逆转电针的上述作用。结论电针治疗可激活A2AR。A2AR拮抗剂SCH58261的作用提示，抑制破骨细胞的形成、抑制肿瘤坏死因子-α、RANK1和NF-κB的表达以及上调ERK1/2均依赖于电针诱导的A2AR的激活。因此，这些在炎症和骨侵蚀中具有明确作用的通路可能至少部分参与了电针抑制滑膜炎和破骨细胞形成的中介作用。
Background This study was to investigate the role of adenosine A2A receptors (A2AR) in inhibiting the effect of electroacupuncture (EA) on osteoclastogenesis in collagen-induced arthritis (CIA). Methods Wistar rats were divided into four groups: sham-control group, CIA-control group, CIA-EA group, and CIA-EA-SCH58261 (A2AR antagonist) group. We detected tumor necrosis factor-α (TNF-α), nuclear transcription factor-κB (NF-κB), receptor activator of NF-κB ligand (RANKL), protein kinase A (PKA), and extracellular regulatory protein kinase 1/2 (ERK1/2) in peripheral blood by ELISA. PKA, ERK1/2, and NF-κB in ankle joints were determined by western blotting. We evaluated the arthritis damage by histological examination and determined the number of osteoclasts by tartrate-resistant acid phosphatase (TRAP) staining. Results EA treatment downregulated the expression of TNF-α, RANKL, PKA, ERK1/2, and NF-κB in peripheral blood but increased the levels of PKA and ERK1/2 in ankle joints. Importantly, EA treatment reduced bone erosion as evidenced by the histological findings and inhibited osteoclastogenesis as revealed by TRAP staining. All these effects of the EA treatment were reversed by combining EA treatment with the A2AR antagonist SCH58261. Conclusion Our data suggest that EA treatment activated A2AR. The effects of the A2AR antagonist SCH58261 suggest that the inhibition of osteoclast formation, the inhibition of TNF-α, RANKL, and NF-κB expression, and the increase of ERK1/2 are all dependent on this EA-induced A2AR activation. It is therefore likely that these pathways with clearly defined roles in inflammation and bone erosion are at least partially involved in the mediation of the inhibition of synovitis and osteoclast formation induced by EA.