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

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.

• Authors: Yani Wang, Rui Liu, Pengfei Zhao, Qian Zhang, Yingheng Huang, Lei Wang, Chengyin Lv, Nan Che, Wenfeng Tan, Miaojia Zhang
• Journal: Clinical rheumatology (Clin Rheumatol) Vol. 41 Issue 1 Pg. 255-264 (Jan 2022) ISSN: 1434-9949 [Electronic] Germany
• PMID: 34387761 (Publication Type: Journal Article)
• Copyright: © 2021. International League of Associations for Rheumatology (ILAR).

Chemical References

• ADIPOR1 protein, human
• Receptors, Adiponectin
• adiponectin receptor 1, mouse

Topics

• Animals
• Arthritis, Experimental (drug therapy)
• Arthritis, Rheumatoid (drug therapy)
• Fibroblasts
• Humans
• Inflammation
• Mice
• Receptors, Adiponectin (antagonists & inhibitors, genetics)
• Signal Transduction
• Synovial Membrane