Rab44-knockout mice exhibit reduced progression of inflammation in collagen antibody-induced arthritis

Abstract Objective:Rheumatoid arthritis (RA) is an autoimmune disease characterized by immune cell-mediated joint inflammation and subsequent osteoclast-dependent bone destruction. This study aimed to investigate whether Rab44 is involved in RA because Rab44 is predominantly distributed in immune cells and osteoclasts. Methods: Collagen antibody-induced arthritis (CAIA) was induced in Rab44-knockout (KO) and wild type (WT) mice. Arthritis severity was assessed daily for 4–9 days by macroscopic observation. Histopathological analysis, real-time PCR analysis for gene expression, immunohistochemical analysis, and µ-computed tomography were performed. Results: Compared to 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 inflammation, cartilage turnover, bone formation and bone absorption markers. Rab44-KO CAIA mice exhibited predominant infiltration of M2-type macrophages at the 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.