Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Impaired Development of Collagen Antibody-Induced Arthritis in Rab44-Deficient Mice

Version 1 : Received: 18 September 2024 / Approved: 18 September 2024 / Online: 18 September 2024 (15:11:03 CEST)

How to cite: Yamaguchi, Y.; Kadowaki, T.; Sakai, E.; Noguromi, M.; Oyakawa, S.; Tsukuba, T. Impaired Development of Collagen Antibody-Induced Arthritis in Rab44-Deficient Mice. Preprints 2024, 2024091444. https://doi.org/10.20944/preprints202409.1444.v1 Yamaguchi, Y.; Kadowaki, T.; Sakai, E.; Noguromi, M.; Oyakawa, S.; Tsukuba, T. Impaired Development of Collagen Antibody-Induced Arthritis in Rab44-Deficient Mice. Preprints 2024, 2024091444. https://doi.org/10.20944/preprints202409.1444.v1

Abstract

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. In this study, we induced CAIA in Rab44-knockout (KO) mice to investigate the effects of Rab44 on inflammation, cell filtration, and bone destruction. 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 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. These results indicate that Rab44 deficiency reduces the progression of inflammation in CAIA in mice.

Keywords

Rab44; collagen antibody-induced arthritis; immune cells; osteoclasts

Subject

Biology and Life Sciences, Immunology and Microbiology

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