Comparative Study of Normal and Rheumatoid Arthritis Fibroblast-Like Synoviocytes Proliferation under Cyclic Mechanical Stretch: Role of Prostaglandin E₂

Abstract

Fibroblast-like synoviocytes (FLSs) are one of the main contributors of prostaglandin E₂ (PGE₂) in the hyperplastic synovium of rheumatoid arthritis (RA) patients. cyclooxygenase-2 (COX-2)/PGE₂ pathway is involved in the proliferation of several cell types. We have previously shown that mechanical stretch affects COX-2 and PGE₂ production in human RA FLSs; however, its role in cell proliferation remains to be elucidated. In this study, a comparison is drawn between human RA and normal FLSs to understand the role of mechanical stretch and PGE₂ on the proliferation of FLSs. The results showed that physiological level (6%, 1 Hz) of cyclic mechanical stretch significantly decreased the proliferation of RA FLSs but not normal FLSs, while the induction of apoptosis was not observed by stretch in either RA or normal FLSs. IL-1β (5 ng/ml)-induced COX-2/PGE₂ levels are downregulated by stretch in RA FLSs only. Further investigation showed that high concentration (100 and 500 ng/ml) of PGE₂ significantly induced cell proliferation only in RA FLSs, and this induction failed to be suppressed by stretch. In conclusion, this study demonstrated that elevated levels of PGE₂ in the synovial cavity are involved in the proliferation of RA FLSs, and cyclic mechanical stretch regulates the RA synovial hyperplasia.

• rheumatoid arthritis
• cyclic stretch
• fibroblast-like synoviocytes
• proliferation
• prostaglandin E₂

ACKNOWLEDGMENTS

This study was supported by the National Natural Science Foundation of China, No. 10672195 and No. 11032012; the Innovation and Attracting Talents Program for College and University (“111” Project of China) (B06023); the Fundamental Research Funds for the Central Universities, No. CDJXS11231176; sharing fund of Chongqing University’s large-scale equipment; and the Key Science and Technology Program of CQ CSTC (CSTC, 2009AA5045).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.