Abstract.
Objective: Articular cartilage is an avascular tissue in which chondrocytes are exposed to hypoxic conditions. We previously demonstrated that reactive oxygen species (ROS) induced apoptosis of chondrocytes. We also demonstrated that nitric oxide (NO) was induced when chondrocytes were exposed to hypoxia and that NO inhibited the ROS-induced apoptosis. Hyaluronan (HA) is a high molecular weight glycosaminoglycan whose antioxidative effects have been reported. The purpose of the present study was to determine whether HA synthesis was induced in chondrocytes exposed to hypoxia, and, if so, whether the hypoxia-induced HA synthesis is regulated by NO.
Methods: Bovine articular chondrocytes were used in this study. Levels of HA were determined by the sandwich enzyme-binding assay. Expression of HA synthase (HAS) was determined with reverse transcription-polymerase chain reaction. The production of NO was examined using the Griess reaction. We also determined inducible nitric oxide synthase (iNOS) enzyme synthesis using the histochemistry and Western blot analysis.
Results: Chondrocytes cultured under hypoxic conditions exhibited enhanced HA synthesis. When the NO inhibitors, L-NMMA and L-NAME, were added, the hypoxia-enhanced HA levels in the culture medium were significantly inhibited.
Conclusions: Endogenous NO synthesis plays an important role in hypoxia-enhanced HA synthesis.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Author information
Authors and Affiliations
Corresponding author
Additional information
Received 5 April 2005; returned for revision 8 August 2005; returned for final revision 26 September 2005; accepted by G. Geisslinger 25 October 2005
This work was supported by a research grant from the Scientific Research Fund of the Ministry of Education, Science and Culture of Japan.
Rights and permissions
About this article
Cite this article
Hashimoto, K., Fukuda, K., Yamazaki, K. et al. Hypoxia-induced hyaluronan synthesis by articular chondrocytes: the role of nitric oxide. Inflamm. res. 55, 72–77 (2006). https://doi.org/10.1007/s00011-005-0012-6
Issue Date:
DOI: https://doi.org/10.1007/s00011-005-0012-6