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- Title
SPACIA1/SAAL1 Deletion Results in a Moderate Delay in Collagen-Induced Arthritis Activity, along with mRNA Decay of Cyclin-dependent Kinase 6 Gene.
- Authors
Fujii, Ryoji; Komatsu, Rie; Sato, Tomoo; Seki, Iwao; Konomi, Koji; Aono, Hiroyuki; Niki, Hisateru; Yudoh, Kazuo; Nishioka, Kusuki; Nakajima, Toshihiro
- Abstract
This study was performed to elucidate the molecular function of the synoviocyte proliferation-associated in collagen-induced arthritis (CIA) 1/serum amyloid A-like 1 (SPACIA1/SAAL1) in mice CIA, an animal model of rheumatoid arthritis (RA), and human RA-synovial fibroblasts (RASFs). SPACIA1/SAAL1-deficient mice were generated and used to create mouse models of CIA in mild or severe disease conditions. Cell cycle-related genes, whose expression levels were affected by SPACIA1/SAAL1 small interfering RNA (siRNA), were screened. Transcriptional and post-transcriptional effects of SPACIA1/SAAL1 siRNA on cyclin-dependent kinase (cdk) 6 gene expression were investigated in human RASFs. SPACIA1/SAAL1-deficient mice showed later onset and slower progression of CIA than wild-type mice in severe disease conditions, but not in mild conditions. Expression levels of cdk6, but not cdk4, which are D-type cyclin partners, were downregulated by SPACIA1/SAAL1 siRNA at the post-transcriptional level. The exacerbation of CIA depends on SPACIA1/SAAL1 expression, although CIA also progresses slowly in the absence of SPACIA1/SAAL1. The CDK6, expression of which is up-regulated by the SPACIA1/SAAL1 expression, might be a critical factor in the exacerbation of CIA.
- Subjects
ARTHRITIS; MESSENGER RNA; CYCLIN-dependent kinases; SYNOVITIS; CELL cycle; CELL proliferation
- Publication
International Journal of Molecular Sciences, 2018, Vol 19, Issue 12, p3828
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms19123828