Inflammation Research

, Volume 64, Issue 3–4, pp 243–252 | Cite as

Hyaluronan suppresses mechanical stress-induced expression of catabolic enzymes by human chondrocytes via inhibition of IL-1β production and subsequent NF-κB activation

  • Masatsugu Ozawa
  • Keiichiro Nishida
  • Aki Yoshida
  • Taichi Saito
  • Ryozo Harada
  • Takahiro Machida
  • Toshifumi Ozaki
Original Research Paper



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.

Materials and methods

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-1β 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-κB (NF-κB) was examined by ELISA and immunocytochemistry, and phosphorylation of NF-κB was examined by western blotting.


HA inhibited mRNA expression of ADAMTS-4, -5, and MMP13 after 24 h CTS via inhibition of IL-1β secretion and NF-κB 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-κB–IL-1β pathway, but did not suppress mechanical stress-induced RUNX-2 signaling.


Chondrocyte Hyaluronan Mechanical stress Aggrecanase NF-κB RUNX-2 


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Copyright information

© Springer Basel 2015

Authors and Affiliations

  • Masatsugu Ozawa
    • 1
  • Keiichiro Nishida
    • 2
  • Aki Yoshida
    • 1
  • Taichi Saito
    • 3
  • Ryozo Harada
    • 1
  • Takahiro Machida
    • 1
  • Toshifumi Ozaki
    • 1
  1. 1.Department of Orthopaedic SurgeryOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayama CityJapan
  2. 2.Department of Human MorphologyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayama CityJapan
  3. 3.Department of Orthopaedic SurgeryAko Central HospitalAkoJapan

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