PER2 is downregulated by the LPS-induced inflammatory response in synoviocytes in rheumatoid arthritis and is implicated in disease susceptibility

Lee,Hwayoung; Nah,Seong‑Su; Chang,Sung‑Hae; Kim,Hyung‑Ki; Kwon,Jun‑Tack; Lee,Sanghyun; Cho,Ik‑Hyun; Lee,Sang  Won; Kim,Young  Ock; Hong,Seung‑Jae; Kim,Hak‑Jae

doi:10.3892/mmr.2017.6578

PER2 is downregulated by the LPS-induced inflammatory response in synoviocytes in rheumatoid arthritis and is implicated in disease susceptibility

Authors:
- Hwayoung Lee
- Seong‑Su Nah
- Sung‑Hae Chang
- Hyung‑Ki Kim
- Jun‑Tack Kwon
- Sanghyun Lee
- Ik‑Hyun Cho
- Sang Won Lee
- Young Ock Kim
- Seung‑Jae Hong
- Hak‑Jae Kim
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Affiliations: Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Chungcheongnam 31151, Republic of Korea, Division of Rheumatology, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Cheonan, Chungcheongnam 31151, Republic of Korea, Department of Integrative Plant Science, Chung‑Ang University, Anseong, Gyeonggi 17546, Republic of Korea, Department of Convergence Medical Science, Brain Korea 21 Plus Program and Institute of Korean Medicine, College of Oriental Medicine, Kyung Hee University, Seoul 02453, Republic of Korea, Department of Development of Ginseng and Medical Plants Research Institute, Rural Administration, Eumseong, Chungcheongbuk 27709, Republic of Korea, Division of Rheumatology, Department of Internal Medicine, School of Medicine, Kyung Hee University, Seoul 02453, Republic of Korea
Published online on: May 11, 2017 https://doi.org/10.3892/mmr.2017.6578
Pages: 422-428

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Abstract

The clinical symptoms of rheumatoid arthritis (RA) present with circadian variation, with joint stiffness and pain more prominent in the early morning. The mammalian clock genes, which include circadian locomotor output cycles kaput, brain and muscle Arnt-like protein 1, period and cryptochrome, regulate circadian rhythms. In order to identify the association between genetic polymorphisms in the circadian clock gene period 2 (PER2) and RA, the present study genotyped three PER2 single nucleotide polymorphisms (SNPs), rs934945, rs6754875, and rs2304674, using genetic information from 256 RA patients and 499 control subjects. Primary cultured rheumatoid synovial cells were stimulated with 10 µM lipopolysaccharide (LPS). Total protein was then extracted from the synovial cells following 12 and 24 h, and PER2 protein expression was assayed by immunoblotting. The rs2304674 SNP demonstrated a significant association with susceptibility to RA following Bonferroni correction. However, statistical analysis indicated that the SNPs were not associated with any clinical features of patients with RA. Immunoblotting analysis demonstrated that PER2 protein expression was decreased by LPS‑induced inflammation in RA synovial cells; however, this was not observed in normal synovial cells. The results suggest that the PER2 gene may be a risk factor for RA, and expression of the PER2 protein may be affected by inflammation. Therefore, PER2 may contribute to the pathogenesis of RA.

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