Effects of umbilical cord-derived mesenchymal stem cells on matrix metalloproteinases secreted by fibroblast-like synoviocytes from rheumatoid arthritis / 中华风湿病学杂志

ABSTRACT

Objective To explore the effects of umbilical cord-derived mesenchymal stem cells (UCMSCs) on fibroblast-like synoviocytes(FLSs) from patients with rheumatoid arthritis(RA). Methods collagen-induced arthritis(CIA) models were developed on Wistar rats and 1 ×106 UCMSCs were given by intravenous injection from tail vein on the 17th day. On day 42, rats were sacrificed and synovial tissues were obtained to detect matrix metalloproteinase (MMP)-1, MMP-3 and MMP-13. Synovial tissues from patients with RA and osteoarthritis(OA) treated by knee arthroplasty were used to isolate FLSs. RNA of FLSs were extracted to compare MMP-1, MMP-3 and MMP-13 expression. FLSs and UCMSCs were cocultured through transwell for 72 hours. Then levels of MMPs were compared in the supernatants by Luminex. The MMPs expressed by FLSs and soluble factors expressed by MSCs were detected by real time-polymerase chain reaction(PCR). After adding antibodies to soluble factors, the MMPs expressions of RA FLSs were compared. Results MMP-1 (6.9±5.4, 1.3±1.4, P 22±21, 22±26, P<0.05) expression were inhibited by UCMSCs in vivo. In vitro, MMP-1 (1.8±0.9, 0.9±0.7, t=2.44, P<0.05), MMP-3(2.6±1.7, 1.1±1.0, t=2.25, P<0.05) and MMP-13(2.4±2.3, 0.6±0.7, t=2.37, P<0.05) levels were higher in RA than OA FLSs. After coculture, MMP-13(1.3±1.2, 0.9±1.2, t=3.63, P<0.05) expressed by FLSs were down-regulated, however MMP-1 (1.5±1.4, 6.6±6.0, t=3.90, P<0.05) and MMP-3 (7±17, 22±35, t=2.86, P<0.05) were up-regulated when analyzed by paired t-test. Soluble factors such as I-DO, HGF and IL-10 were elevated. Anti-IL-10 antibody could decrease the function of UCMSCs by inhibiting MMP-13 expression in RA FLSs. Conclusion UCMSCs ameliorates RA by secreting soluble factor IL-10, which may inhibit MMPs expressed by FLSs.