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Clinical Rheumatology
Published in: Clinical Rheumatology 1/2022

01-01-2022 | Arthritis | Original Article

Blockade of adiponectin receptor 1 signaling inhibits synovial inflammation and alleviates joint damage in collagen-induced arthritis

Authors: Yani Wang, Rui Liu, Pengfei Zhao, Qian Zhang, Yingheng Huang, Lei Wang, Chengyin Lv, Nan Che, Wenfeng Tan, Miaojia Zhang

Published in: Clinical Rheumatology | Issue 1/2022

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Abstract

Objectives

Adiponectin (AD) highly expressed in synovial tissue correlates closely with progressive bone erosion in rheumatoid arthritis (RA). However, it remains unknown whether AD receptor mediates the pathogenesis of RA. This study aimed to investigate the effects of adiponectin receptor 1 (AdipoR1) signaling on synovial inflammation and joint damage in collagen-induced arthritis.

Methods

AD and AdipoR1 expression in synovial tissue of RA and osteoarthritis (OA) patients were tested by PCR and western blotting. The frequency of AdipoR1 on RA synovial fibroblasts (RASFs) was examined by flow cytometry after stimulation with AD, IL-6, or TNF-α. AdipoR1 was knocked down in human RASF cell line (MH7A) and CIA mice joints using lentiviral particles carrying the AdipoR1 short hairpin RNA (shAdipoR1). Both the proliferation and apoptosis of MH7A and the secretion of inflammatory factors from MH7A were examined in vitro. The therapeutic effect of local AdipoR1 inhibition on CIA mice was assessed in vivo.

Results

Both the expression of AD and AdipoR1 were significantly higher in RA synovial tissue. AdipoR1 on RASFs was upregulated by AD. Silencing AdipoR1 remarkably reduced lipopolysaccharides-induced proliferation and promoted the apoptosis of MH7A. Moreover, AdipoR1 knockdown inhibited the release of inflammatory factors in vitro. In CIA mice, local AdipoR1 inhibition effectively decreased joint inflammation and alleviated bone destruction via suppressing RANKL and RANKL/OPG ratio in vivo.

Conclusions

AdipoR1 signaling participates in the process of synovial inflammation and joint damage in CIA. Local blockade of AdipoR1 might be a new target for the clinical treatment of RA.
Key points
• Local AdipoR1 inhibition decreased joint inflammation and alleviated bone destruction in CIA.
Appendix
Available only for authorised users
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Metadata
Title
Blockade of adiponectin receptor 1 signaling inhibits synovial inflammation and alleviates joint damage in collagen-induced arthritis
Authors
Yani Wang
Rui Liu
Pengfei Zhao
Qian Zhang
Yingheng Huang
Lei Wang
Chengyin Lv
Nan Che
Wenfeng Tan
Miaojia Zhang
Publication date
01-01-2022
Publisher
Springer International Publishing
Published in
Clinical Rheumatology / Issue 1/2022
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-021-05846-w

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