PMID- 30956681 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220408 IS - 1741-427X (Print) IS - 1741-4288 (Electronic) IS - 1741-427X (Linking) VI - 2019 DP - 2019 TI - Adenosine A2A Receptor Mediates Inhibition of Synovitis and Osteoclastogenesis after Electroacupuncture in Rats with Collagen-Induced Arthritis. PG - 4617464 LID - 10.1155/2019/4617464 [doi] LID - 4617464 AB - 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-alpha (TNF-alpha), nuclear transcription factor-kappaB (NF-kappaB), receptor activator of NF-kappaB 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-kappaB 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-alpha, RANKL, PKA, ERK1/2, and NF-kappaB 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-alpha, RANKL, and NF-kappaB 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. FAU - Du, Zhong-Heng AU - Du ZH AD - Department of Acupuncture, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. FAU - Zhang, Chun-Wu AU - Zhang CW AD - Department of Traditional Chinese Orthopedics & Traumatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. FAU - Xie, Wen-Xia AU - Xie WX AD - Department of Acupuncture, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. FAU - Chen, Yong AU - Chen Y AD - Department of Acupuncture, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. FAU - Cong, Wen-Jie AU - Cong WJ AD - Department of Acupuncture, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. FAU - Wang, Ze-Dong AU - Wang ZD AD - Department of Acupuncture, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. FAU - Wang, En-Pei AU - Wang EP AD - Department of Acupuncture, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. FAU - Wu, Guang-Yu AU - Wu GY AUID- ORCID: 0000-0002-8273-1741 AD - Department of Traumatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. FAU - Ye, Tian-Shen AU - Ye TS AUID- ORCID: 0000-0003-1745-8918 AD - Department of Acupuncture, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. LA - eng PT - Journal Article DEP - 20190306 PL - United States TA - Evid Based Complement Alternat Med JT - Evidence-based complementary and alternative medicine : eCAM JID - 101215021 PMC - PMC6431381 EDAT- 2019/04/09 06:00 MHDA- 2019/04/09 06:01 PMCR- 2019/03/06 CRDT- 2019/04/09 06:00 PHST- 2019/01/12 00:00 [received] PHST- 2019/02/26 00:00 [accepted] PHST- 2019/04/09 06:00 [entrez] PHST- 2019/04/09 06:00 [pubmed] PHST- 2019/04/09 06:01 [medline] PHST- 2019/03/06 00:00 [pmc-release] AID - 10.1155/2019/4617464 [doi] PST - epublish SO - Evid Based Complement Alternat Med. 2019 Mar 6;2019:4617464. doi: 10.1155/2019/4617464. eCollection 2019.