Abstract
The imbalance between proliferation and apoptosis of fibroblast-like synoviocytes (FLSs) has been the main cause of rheumatoid arthritis (RA) synovial hyperplasia. Our previous study confirmed that the cyclic mechanical stimulation (CMS) inhibited the proliferation of RA FLSs, but the underlying mechanisms are still unclear. This study aimed to investigate these underlying mechanisms. The in vitro cultured human RA FLSs were subjected to CMS (6%, 1.0 Hz). Cell cycle was detected by flow cytometry. The expression of cyclin D1, cyclin E1, CDK-2 and p27 was detected by reverse transcription-polymerase chain reaction (RT-PCR). MTS assay was used to detect cell viability. Cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) levels in RA FLSs were detected by western blotting and enzyme-linked immunosorbent assay (ELISA), respectively. The results showed that CMS significantly inhibited the cell cycle transformation of RA FLSs from G1 phase to S phase, which significantly decreased the cell proliferation index. Meanwhile, both cyclin E1 and CDK-2 gene expressions were significantly decreased, p27 gene expression was increased, and no significant change was observed in the expression of cyclin D1. The inhibition of COX-2/PGE2 pathway in RA FLSs by celecoxib treatment showed no effect on the inhibition of RA FLSs proliferation by CMS. In conclusion, CMS inhibited the proliferation of RA FLSs by modulating the expression of cell cycle-related molecules such as cyclin E1, CDK2 and p27 to arrest cell cycle transformation, which is independent of COX-2/PGE2 signaling pathway.