Osteoarthritis (OA) is a progressive and disabling disorder, characterized by synovial inflammation and joint effusion. This study aimed to explore the role of stanniocalcin-1 (STC1) in the development of OA by regulating the survival and inflammation of fibroblast-like synovial (FLS) cells.
Microarray analyses were adopted to screen differentially expressed genes (DEGs) related to OA, and regulatory microRNA (miR) was also identified. Synovial tissue samples from patients with OA and healthy individuals were obtained to determine the expression levels of miR-454, STC1, IL-6, IL-8, and MMP3/13. The targeted relationship between miR-454 and STC1 was verified by dual-luciferase reporter gene assay. With the treatment of miR-454 mimic and STC1 overexpression vector, the effect of miR-454 and STC1 on FLS cell viability and apoptosis as well as production of inflammatory cytokines were tested.
STC1 with aberrant low expression was screened from GSE1919 profile in OA. STC1 was found to be downregulated in OA-FLS tissues and cells. STC1 overexpression inhibited OA-FLS cell viability but induced apoptosis of OA-FLS cells. Moreover, STC1 overexpression decreased levels of IL-6, IL-8, and MMP3/13, suggesting that STC1 overexpression suppressed inflammatory reactions. In addition, miR-454 blocked the inhibitory effects of STC1 overexpression on OA-FLS cell viability and inflammatory reaction and exerted a promotion effect of STC1 overexpression on apoptosis of OA-FLS cells.
Taken together, the results revealed that upregulation of STC1 could repress proliferation of OA-FLS cells and inflammatory reaction, and enhance apoptosis of OA-FLS cells, which was negatively regulated by miR-454.