Hyaluronan suppresses enhanced cathepsin K expression via activation of NF-κB with mechanical stress loading in a human chondrocytic HCS-2/8 cells.

Cathepsin K is a protease known to be involved in not only bone remodeling and resorption, but also articular cartilage degradation that leads to osteoarthritis (OA). Hyaluronan (HA) plays a pivotal role in maintaining homeostasis within articular chondrocytes. Intra-articular supplementation of high molecular weight hyaluronan (HMW-HA) has been widely used in OA treatment. However, its prospective mechanism of action is still unclear. In this study, we examined the suppressive effect of HA on enhanced cathepsin K expression induced by mechanical stress loading. A human chondrocytic HCS-2/8 cells were cultured in silicon chambers and subjected to cyclic tensile stress (CTS) loading. CTS loading significantly increased messenger ribonucleic acid and protein expression of cathepsin K, which appeared to be suppressed by pre-treatment with HMW-HA. Activation of nuclear factor-kappa B (NF-κB) was induced by CTS loading, and suppressed by pre-treatment with HMW-HA. Helenalin, a chemical inhibitor of NF-κB, clearly suppressed the enhanced expression of cathepsin K, as well as NF-κB activation induced by CTS loading. The suppressive effect of HMW-HA on enhanced cathepsin K expression via NF-κB inhibition impacts the effectiveness of HMW-HA in OA treatment. Our findings provide new evidence supporting the biological effectiveness of intra-articular HMW-HA injections for treatment of OA.