Immunomodulatory roles of metalloproteinases in rheumatoid arthritis

Yanqin Bian; Zheng Xiang; Yaofeng Wang; Qing Ren; Guoming Chen; Bei Xiang; Jianye Wang; Chengbo Zhang; Shaoqiang Pei; Shicheng Guo; Lianbo Xiao

doi:10.3389/fphar.2023.1285455

Immunomodulatory roles of metalloproteinases in rheumatoid arthritis

Front Pharmacol. 2023 Nov 15:14:1285455. doi: 10.3389/fphar.2023.1285455. eCollection 2023.

Authors

Yanqin Bian^#^{1

2}, Zheng Xiang^#^{1

2}, Yaofeng Wang^#^{1

2}, Qing Ren³, Guoming Chen³, Bei Xiang², Jianye Wang^{1

2}, Chengbo Zhang^{1

2}, Shaoqiang Pei^{1

2}, Shicheng Guo⁴, Lianbo Xiao^{1

2}

Affiliations

¹ Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China.
² Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
³ Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.
⁴ Department of Medical Genetics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States.

^# Contributed equally.

Abstract

Rheumatoid arthritis (RA) is a chronic, autoimmune pathology characterized by persistent synovial inflammation and gradually advancing bone destruction. Matrix metalloproteinases (MMPs), as a family of zinc-containing enzymes, have been found to play an important role in degradation and remodeling of extracellular matrix (ECM). MMPs participate in processes of cell proliferation, migration, inflammation, and cell metabolism. A growing number of persons have paid attention to their function in inflammatory and immune diseases. In this review, the details of regulation of MMPs expression and its expression in RA are summarized. The role of MMPs in ECM remodeling, angiogenesis, oxidative and nitrosative stress, cell migration and invasion, cytokine and chemokine production, PANoptosis and bone destruction in RA disease are discussed. Additionally, the review summarizes clinical trials targeting MMPs in inflammatory disease and discusses the potential of MMP inhibition in the therapeutic context of RA. MMPs may serve as biomarkers for drug response, pathology stratification, and precision medicine to improve clinical management of rheumatoid arthritis.

Keywords: angiogenesis; bone destruction; matrix metalloproteinases; rheumatoid arthritis; target.

Publication types

Review

Grants and funding

The authors declare that no financial support was received for the research, authorship, and/or publication of this article. This work was funded by the National Natural Science Funds of China (82004166), Shanghai Municipal Science and Technology Commission (22ZR1453100, 21Y11921500), Health Commission project of Changning District in Shanghai (20194Z001), Outstanding Traditional Chinese Medicine (TCM) Reserve Talents of Shanghai University of Traditional Chinese Medicine (2020M) and Training Program for High-caliber Talents of Clinical Research at Affiliated Hospital of SHUTCM (2023LCRC24).