Osteoarthritis (OA) is a destructive joint disorder with articular cartilage erosions and fibrillations, as well as clustering and proliferation of articular chondrocytes. ecently, aggrecaneses, aggecan-degrading metalloproteinases, are considered to play a key role in the progression of OA. Among aggrecaneses, ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) gene family, such as ADAMTS1,4,5,8,9 and 15 are known to have aggrecanese activity. The purpose of this study was to investigate the mechanisms by which high molecular weight hyaluronic Acid (HMW-HA) regulates ADAMTS4 expression induced by IL-1β in human fibroblast-like synoviocytes (HFLS) cells.
Method:
HFLS cells were treated with IL-1β and HMW-HA. In some experiments, HFLS cells were pre-treated with a variety of inhibitors of signaling pathways prior to the addition of IL-1β. Expression of ADAMTS4 were monitored by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The localization and secretion of ADAMTS4 protein were determined using immunofluorescence microscopy and ELISA.
Result:
HMW-HA suppressed both mRNA and protein expression of ADAMTS4 induced by IL-1β. HMW-HA also inhibited phosphorylation of p38 MAPK, ERK, JNK proteins induced by IL-1β. Furthermore, inhibition of the p38 MAPK pathway by chemical inhibitors suppressed ADAMTS4 mRNA expression induced by IL-1β.
Conclusion:
We found that HMW-HA down-regulated the ADAMTS4 expression in HFLS cells induced by IL-1β via inhibition of p38 MAPK signaling pathway, suggesting that HMW-HA may play an important role as a regulation factor in synovial tissue inflammation.