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Abstract Presented at the 26th Annual Meeting of the Arthroscopy Association of North America| Volume 23, ISSUE 6, SUPPLEMENT , e25, June 2007

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Chondroprotective Effects of Hyaluronic Acid Following Oxidative Stress (SS-49)

      Summary

      The purpose of current study was to examine the mechanisms of chondroprotective effects of hyaluronic acid following reactive oxygen and nitrogen species -induced stress. We find that hyaluronic acid protects human chondrocyte mitochondria from oxidative stress by decrease of mitochondrial DNA damage and enhancing mitochondrial DNA repair. Hyaluronic acid pretreatment of human chondrocytes prevented mitochondrial transcription and ATP levels decrease following oxidative stress. Also hyaluronic acid prevented apoptosis induced in human chondrocytes following exposure to ROS and RNS by direct prevention of cytochrome c release and activation of caspase 9.

      Purpose

      The intra-articular injection of hyaluronic acid was originally used in the treatment of osteoarthritis to increase the viscosity of synovial liquid. However, recent findings suggest that the activity of HA cannot be solely explained by its biomechanical properties. Current study was performed to determine the mechanisms of chondroprotective action of hyaluronic acid on articular chondrocytes following reactive oxygen and nitrogen species generation as observed during osteoarthritis development. Chondrocyte mitochondrial function, apoptosis and viability following oxidative stress were main targets of present investigation.

      Methods

      All work was performed on primary articular chondrocyte cultures. Reactive oxygen species were generated by xanthine oxidase/hypoxanthine exposure, reactive nitrogen species by peroxynitrite. DNA damage and repair were studied by quantitative Southern blot analysis; mitochondrial dysfunction was evaluated by Northern blot analysis of mitochondrial transcription and changes in ATP levels by bioluminescence assay. Apoptosis was evaluated by quantitation of apoptotic cells following DAPI staining, cytochrome c release, and caspases activation. Cell viability was evaluated by MTT assay.

      Results

      Hyaluronic acid protects human chondrocyte mitochondria by amelioration of mitochondrial DNA damage and enhancing mtDNA repair. Hyaluronic acid preserved mitochondrial transcription and ATP levels following oxidative stress. Also HA pretreatment led to increase of chondrocyte viability and decrease of apoptosis following xanthine oxidase/hypoxanthine and peroxynitrite treatment.

      Conclusions

      Mitochondria are important targets of hyaluronic acid chondroprotective action.