Research Articles

Electroacupuncture stimulating Zusanli (ST36), Sanyinjiao (SP6) in mice with collagen-induced arthritis leads to adenosine A2A receptor-mediated alteration of p38α mitogen-activated protein kinase signaling and inhibition of osteoclastogenesis

  • Zhongheng DU ,
  • Wenjie CONG ,
  • Kejing TANG ,
  • Qiqi ZHENG ,
  • Zhiwei SONG ,
  • Yong CHEN ,
  • Su YANG ,
  • Chunwu ZHANG ,
  • Tianshen YE
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  • 1 Department of Acupuncture, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
    2 Department of Traditional Chinese Orthopedics & Traumatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
    3 Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China

Received date: 2022-06-22

  Accepted date: 2022-09-21

  Online published: 2023-11-01

Supported by

Mechanism of Adenosine A2A Receptor Modulate Electroacupuncture Inhibiting Osteoclast Formation in Mice with Collagen-Induced Arthritis(81674053);Role of P38 MAPK Pathway in the Inhibition of CIA Osteoclast Differentiation by Electroacupuncture via Adenosine Pathway(LY20H270015);Electroacupuncture of Mice with CIA Mitigate Joint Damage by the p38MAPK Pathway(Y20190198);Electroacupuncture of Mice with CIA Mitigate Joint Damage by the p38MAPK Pathway(FHY2019021)

Abstract

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulating Zusanli (ST36), Sanyinjiao (SP6) on inhibition of osteoclastogenesis and the role of the adenosine A2A receptor (A2AR) and the p38α Mitogen-Activated Protein Kinase (MAPK) signaling pathway in mediating this effect.
METHODS: Mice with collagen induced arthritis (CIA) received different treatments. Immunohistochemistry and western blotting were used to determine the levels of multiple signaling molecules in these joints [receptor activator of nuclear transcription factor-κB (NF-κB) ligand (RANKL), receptor activator of NF-κB (RANK), tumor necrosis factor receptor associated factor 6 (TRAF6), p38α, NF-κB, and nuclear factor of activated T cells C1 (NFATc1)]. Osteoclasts were identified using tartrate-resistant acid phosphatase (TRAP) staining.
RESULTS: The immunohistochemistry results indicated upregulation of p38α, NF-κB, and NFATc1 in the CIA-control and CIA-EA-SCH58261 groups, but reduced levels in the CIA-EA group. Western blotting indicated upregulation of RANKL, RANK, TRAF6, p38α, NF-κB, and NFATc1 in the CIA-control and CIA-EA-SCH58261 groups, but reduced expression in the CIA-EA group. Osteoclasts were more abundant in the CIA-control and CIA-EA-SCH58261 groups than in the CIA-EA group.
CONCLUSIONS: EA treatment enhanced the A2AR activity and inhibited osteoclast formation by inhibition of RANKL, RANK, TRAF6, p38α, NF-κB, and NFATc1. SCH58261 reversed the effect of EA. These results suggest that EA regulated p38α-MAPK signaling by increasing A2AR activity, which inhibited osteoclastogenesis.

Cite this article

Zhongheng DU , Wenjie CONG , Kejing TANG , Qiqi ZHENG , Zhiwei SONG , Yong CHEN , Su YANG , Chunwu ZHANG , Tianshen YE . Electroacupuncture stimulating Zusanli (ST36), Sanyinjiao (SP6) in mice with collagen-induced arthritis leads to adenosine A2A receptor-mediated alteration of p38α mitogen-activated protein kinase signaling and inhibition of osteoclastogenesis[J]. Journal of Traditional Chinese Medicine, 2023 , 43(6) : 1103 -1109 . DOI: 10.19852/j.cnki.jtcm.2023.06.001

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