Hyaluronan suppresses mechanical stress-induced expression of catabolic enzymes by human chondrocytes via inhibition of IL-1[beta] production and subsequent NF-[kappa]B activation

• Published in: Inflammation research 2015-04, Vol.64 (3-4), p.243
• Main Authors: Ozawa, Masatsugu, Nishida, Keiichiro, Yoshida, Aki, Saito, Taichi, Harada, Ryozo, Machida, Takahiro, Ozaki, Toshifumi
• Format: Article
• Language: English
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-015-0804-2

To investigate the inhibitory effect of hyaluronan (HA) on mechanical stress- induced expression of a disintegrin and metalloproteinase with thrombospondin type1 motifs (ADAMTS)-4, -5 and matrix metalloproteinase (MMP)-13 by human chondrocytes. Normal human articular chondrocytes were pre-incubated with or without 1.0 mg/mL HA (2700 kDa) for 12 h at 37 °C in stretch chambers, then they were exposed to uni-axial cyclic tensile strain (CTS, 0.5 Hz, 10 % elongation). The expression of ADAMTS-4, -5, and MMP-13 were analyzed by real-time polymerase chain reaction and Immunocytochemistry. The concentration of IL-1[beta] in the supernatant was measured using enzyme-linked immunosorbent assay (ELISA). The nuclear translocation of runt-related transcription factor 2 (RUNX-2) and nuclear factor-[kappa]B (NF-[kappa]B) was examined by ELISA and immunocytochemistry, and phosphorylation of NF-[kappa]B was examined by western blotting. HA inhibited mRNA expression of ADAMTS-4, -5, and MMP13 after 24 h CTS via inhibition of IL-1[beta] secretion and NF-[kappa]B activation. However, HA failed to inhibit CTS-induced RUNX-2 expression and subsequent expression of ADAMTS-5 and MMP-13 1 h after CTS. Our results demonstrated that HA significantly suppressed mechanical stress-induced expression of catabolic proteases by inhibition of the NF-[kappa]B-IL-1[beta] pathway, but did not suppress mechanical stress-induced RUNX-2 signaling.