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薬理と治療
Abstract
Objective The present study was designed to examine the influence of hyaluronic acid(HA) on the ability of synoviocytes to produce thioredoxin(TRX), which is one of important endogenous anti-oxidative molecule, in response to H2O2 stimulation in vitro. Methods Synoviocytes(1×105 cells╱mL)derived from an osteoarthritis patient were stimulated with 25.0μM H2O2 in the presence of various concentrations of HA for 24 hours. The levels of TRX in culture supernatants were examined by ELISA. To examine the influence of HA on transcription factor, STAT6, activation and TRX mRNA expression, synoviocytes were also cultured in a similar manner for 6 and 12 hours, respectively. STAT6 activation was examined by ELISA and the levels of mRNA expression were real-time RT-PCR. We also examined the influence of HA on TRX protein production using a cell-free protein synthesis system Results Addition of HA into cell cultures caused the increase in H2O2-induced TRX production from synoviocytes. The minimum concentration that caused significant increase in TRX production was 2.5 mg╱mL. Although HA at more than 2.5 mg╱mL inhibited STAT6 activation and TRX mRNA expression, which were increased by H2O2 stimulation in synoviocytes, HA enhanced translation of TRX mRNA and results in increase in the production of TRX. Conclusion These results strongly suggest that HA favorably modify the clinical condition of osteoarthritis patients through the increase in the production of TRX, which is responsible for the development of oxidative stress response, from synoviocytes after the stimulation with reactive oxygen species. (Jpn Pharmacol Ther 2022;50:1333‒41)
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