Impaired Development of Collagen Antibody-Induced Arthritis in Rab44-Deficient Mice
Yu Yamaguchi1, Tomoko Kadowaki2, Eiko Sakai1
1Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8588, Japan.
Background:
Rheumatoid arthritis (RA) is an autoimmune disease characterized by immune cell-mediated joint inflammation and subsequent osteoclast-dependent bone destruction. Collagen antibody-induced arthritis (CAIA) is a useful mouse model for examining the inflammatory mechanisms in human RA. Previously, we identified the novel gene Rab44, which is a member of the large Rab GTPase family and is highly expressed in immune-related cells and osteoclasts.
Methods:
In this study, we induced CAIA in Rab44-knockout (KO) mice to investigate the effects of Rab44 on inflammation, cell filtration, and bone destruction.
Results:
Compared with wild-type (WT) mice, Rab44-KO mice showed reduced inflammation in arthritis under CAIA-inducing conditions. Rab44-KO CAIA mice exhibited reduced cell filtration in the radiocarpal joints. Consistent with these findings, Rab44-KO CAIA mice showed decreased mRNA levels of arthritis-related marker genes including genes for inflammation, cartilage turnover, bone formation, and bone absorption markers. Rab44-KO CAIA mice exhibited predominant infiltration of M2-type macrophages at inflammatory sites and reduced bone loss compared to WT CAIA mice.
Conclusions:
These results indicate that Rab44 deficiency reduces the progression of inflammation in CAIA in mice.
