Hyaluronan enhances proteoglycan4 expression in synovial cells

Synovial fluid contains various molecules such as hyaluronan (HA) and proteoglycan4 (PRG4) that play important roles in maintaining proper joint lubrication. However, the interaction between HA and PRG4 remains unclear. We aimed to investigate the effect of high molecular weight hyaluronan (HMW-HA) on the expression of PRG4 and signaling pathways in cultured human fibroblast-like synoviocytes (HFLS).HFLS were treated with hyaluronidase (HAase) prior to addition of HMW-HA. PRG4 expression was significantly increased by HA and significantly down-regulated by HAase treatment; however, the effect of HAase was inhibited by the presence of HMW-HA. HFLS were also treated with an anti-CD44 neutralizing antibody or MEK1/2 inhibitor (U0126) prior to addition of HMW-HA. PRG4 mRNA expression was significantly down-regulated by addition of the anti-CD44 neutralizing antibody or U0126, when compared to the untreated control. Co-treatment with HMW-HA prevented the inhibitory effect of the anti-CD44 antibody but could not prevent the inhibitory effect of U0126 on PRG4 mRNA expression. Thus HMW-HA regulates the expression of PRG4 by a slight interaction with CD44 through MAPK-ERK signaling pathway. Therefore, interaction between HA and PRG4 may be critical for proper lubricating function in the surface of articular cartilage in the TMJ.Clinical trial number: REG1464069KEYWORDS: Fluid lubrication, temporomandibular disorders, osteoarthritis, MAPK signaling, synovial membrane cells