Dantrolene, a stabilizer of the ryanodine receptor, prevents collagen-induced arthritis

Biochem Biophys Res Commun. 2022 Oct 8:624:141-145. doi: 10.1016/j.bbrc.2022.07.111. Epub 2022 Aug 2.

Abstract

Dantrolene inhibits Ca2+ leakage from destabilized ryanodine receptors and therefore may serve as a therapeutic agent against endoplasmic reticulum stress-associated diseases. However, its effectiveness in treating autoimmune diseases remains unclear. Here, we investigated the effect of dantrolene on collagen-induced arthritis (CIA) in mice. Oral administration of dantrolene resulted in significantly lower arthritic scores in both male and female CIA mice than in the control mice. Micro-computed tomographic and histological analyses showed that dantrolene suppressed bone and chondral destruction. The serum levels of anti-type II collagen (CII) IgG were positively correlated with the arthritic scores (r = 0.704, p < 0.01). In addition, the serum levels of anti-CII IgG were significantly lower in the dantrolene group than in the control group (p < 0.05). These results demonstrate that oral administration of dantrolene to CIA mice inhibits the production of serum anti-CII IgG and consequently prevents arthritis. Therefore, dantrolene may be a potential anti-rheumatic drug.

Keywords: Collagen-induced arthritis; Dantrolene; Rheumatoid arthritis; Ryanodine receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental* / pathology
  • Collagen Type II
  • Dantrolene / pharmacology
  • Dantrolene / therapeutic use
  • Female
  • Immunoglobulin G
  • Male
  • Mice
  • Mice, Inbred DBA
  • Ryanodine Receptor Calcium Release Channel

Substances

  • Collagen Type II
  • Immunoglobulin G
  • Ryanodine Receptor Calcium Release Channel
  • Dantrolene