Publication in detail

Int J Mol Sci. 2018 Nov 30;19(12). pii: E3828. doi: 10.3390/ijms19123828.

SPACIA1/SAAL1 Deletion Results in a Moderate Delay in Collagen-Induced Arthritis Activity, along with mRNA Decay of Cyclin-dependent Kinase 6 Gene.

Fuiji, R; Komatsu, R; Sato, T; Seki, I; Konomi, K; Aono, H; Niki, H; Yudoh, K; Nishioka, K; Nakajima, T

Institute of Medical Science, St. Marianna University School of Medicine, Kanagawa 216-8512, Japan. AYUMI Pharmaceutical Corporation, Kyoto 612-8374, Japan. Santen Pharmaceutical Co., Ltd., Osaka 533-8651, Japan. Department of Orthopedic Surgery, St. Marianna University School of Medicine, Kanagawa 216-8511, Japan. Global Health Innovation Policy Program (GHIPP), National Graduate Institute for Policy Studies (GRIPS), Tokyo 106-8677, Japan. Institute of Medical Science, Tokyo Medical University, Tokyo 160-8402, Japan. Misato Marine Hospital, Kochi 781-0112, Japan.

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.

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