impact factor
logo
 

Full Papers

 

Metformin repositioning in rheumatoid arthritis


1, 2, 3, 4, 5, 6, 7, 8, 9, 10

 

  1. Institute for Environment and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Chiba; and Department of Internal Medicine and Rheumatology, School of Medicine, Juntendo University, Tokyo, Japan.
  2. Department of Internal Medicine and Rheumatology, Juntendo University Urayasu Hospital, Chiba, Japan. morimoto@juntendo.ac.jp
  3. Institute for Environment and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan.
  4. Institute for Environment and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan.
  5. Institute for Environment and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan.
  6. Department of Internal Medicine and Rheumatology, Juntendo University Urayasu Hospital, Chiba, Japan.
  7. Department of Internal Medicine and Rheumatology, Juntendo University Urayasu Hospital, Chiba, Japan.
  8. Institute for Environment and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan.
  9. Department of Internal Medicine and Rheumatology, School of Medicine, Juntendo University, Tokyo, Japan.
  10. Department of Internal Medicine and Rheumatology, School of Medicine, Juntendo University, Tokyo, Japan.

CER13443
Full Papers

purchase article

PMID: 32828146 [PubMed]

Received: 13/04/2020
Accepted : 12/06/2020
In Press: 05/08/2020

Abstract

OBJECTIVES:
Metformin is a known therapeutic agent for diabetes. Recently, several reports suggested the possibility of improvement in autoimmune disease and malignancy conditions through the effect of metformin on the immune system. Although there have been reports on the therapeutic effects of metformin on mouse models of collagen-induced arthritis, simulating human rheumatoid arthritis (RA), the effect of metformin on human RA remains unknown. Therefore, we investigated the inhibitory effect of metformin on the pathogenesis of human RA in vitro.
METHODS:
Osteoclastogenesis was evaluated with or without metformin. through tartrate-resistant acid phosphatase staining, osteoclast-specific enzyme expression analysis, and a bone resorption assay. Human fibroblast-like synoviocyte MH7A cells were stimulated with TNF-α, and the expression of proinflammatory cytokines and protease and growth factor genes was evaluated with or without metformin. Metformin has been used to evaluate their potential modulatory effects on cells treated with TNF-α. Moreover, we examined angiogenesis by performing a tube formation assay using human umbilical vein endothelial cells (HUVECs) with or without metformin.
RESULTS:
Osteoclastogenesis was suppressed in the presence of metformin, and the expression of osteoclast-specific genes was reduced. The TNF-α-induced expression of inflammatory cytokines and protease and growth factor genes in MH7A cells was downregulated by metformin. Additionally, the induced formation of tubular networks in HUVECs was also disrupted following treatment with metformin.
CONCLUSIONS:
These results suggest that metformin might improve the pathogenesis of RA, including joint inflammation and destruction. Thus, metformin might be utilised as a potential therapeutic agent in the treatment of RA.

Rheumatology Article