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薬理と治療
Abstract
Objective The present study was designed to examine the influence of glucosamine hydrochloride(GH)on the ability of synoviocytes to produce matrix metalloproteinase(MMP)and tissue inhibitor of metalloproteinase(TIMP)in response to osteopontin(OPN)stimulation in vitro. Methods Synoviocytes(5⊠105 cells╱mL)derived from osteoarthritis patients were stimulated with 330 ng╱mL OPN in the presence of various concentrations of GH for 24 hours. The levels of both MMPs(MMP︱1, ︱2 and︱13)and TIMPs(TIMP︱1, and︱2)in culture supernatants was examined by ELISA. To examine the influence of GH on transcription factor, NF︱κB, activation and mRNA expression for MMPs and TIMPs, synoviocytes(5⊠105 cells╱mL)were also cultured in a similar manner for 4 and 12 hours, respectively. The levels of NF︱κB activation was examined by ELISA. mRNA expression was examined by real︱time RT︱PCR. Results Addition of GH at more than 1.0 mg╱mL into cell cultures suppressed dose dependently the production of MMP︱1, ︱2, and︱13 from synoviocytes after OPN stimulation. Although GH also suppressed the ability of synoviocytes to produce TIMP︱1 and︱2 in response to OPN stimulation, the minimum concentration that caused significant suppression was 1.5 mg╱mL. GH inhibited mRNA expression for both MMPs and TIMPs through the suppression of NF︱κB activation, which were increased by OPN stimulation in synoviocytes. Conclusion These results strongly suggest that GH favorably modify the clinical condition of osteoarthritis patients through the suppression of MMPs and TIMPs production from synoviocytes.
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