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Pyrroloquinoline Quinone Slows Down the Progression of Osteoarthritis by Inhibiting Nitric Oxide Production and Metalloproteinase Synthesis

Abstract

Osteoarthritis (OA) is the most common arthritis and also one of the major causes of joint pain in elderly people. The aim of this study was to investigate the effects of pyrroloquinoline quinone (PQQ) on degenerated-related changes in osteoarthritis (OA). SW1353 cells were stimulated with IL-1β to establish the chondrocyte injury model in vitro. PQQ was administrated into SW1353 cultures 1 h before IL-1β treatment. Amounts of MMP-1, MMP-13, P65, IκBα, ERK, p-ERK, P38, and p-P38 were measured via western blot. The production of NO was determined by Griess reaction assay and reflected by the iNOS level. Meniscal-ligamentous injury (MLI) was performed on 8-week-old rats to establish the OA rat model. PQQ was injected intraperitoneally 3 days before MLI and consecutively until harvest, and the arthritis cartilage degeneration level was assessed. The expressions of MMP-1 and MMP-13 were significantly downregulated after PQQ treatment compared with that in IL-1β alone group. NO production and iNOS expression were decreased by PQQ treatment compared with control group. Amounts of nucleus P65 were upregulated in SW1353 after stimulated with IL-1β, while PQQ significantly inhibited the translocation. In rat OA model, treatment with PQQ markedly decelerated the degeneration of articular cartilage. These findings suggested that PQQ could inhibit OA-related catabolic proteins MMPs expression, NO production, and thus, slow down the articular cartilage degeneration and OA progression. Owing to its beneficial effects, PQQ is expected to be a novel pharmacological application in OA clinical prevention and treatment in the near future.

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ACKNOWLEDGMENTS

This work was supported by National Basic Research Program of China (973 Program, No. 2012CB822104), National Natural Science Foundation of China (31170766, 81171140), Key Project Natural Science Foundation of Jiangsu University and College (No. 11KJA310002), Nantong City Social Development Projects funds (HS2012032), and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Conflict of Interest

The authors of this manuscript have no conflict of interests to declare.

Authors’ Contribution

RT and ST concepted the study, designed experiment and wrote manuscript. PL, XX, XX, ZL helped in animal experiments. YW, YC, YH were involved in cell experiments. XT, CL helped in statistical analysis of data. All authors have read and approved the final manuscript.

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Correspondence to Gan Shen or Dongmei Zhang.

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Tao, R., Wang, S., Xia, X. et al. Pyrroloquinoline Quinone Slows Down the Progression of Osteoarthritis by Inhibiting Nitric Oxide Production and Metalloproteinase Synthesis. Inflammation 38, 1546–1555 (2015). https://doi.org/10.1007/s10753-015-0129-x

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  • DOI: https://doi.org/10.1007/s10753-015-0129-x

KEY WORDS

  • pyrroloquinoline quinone
  • NF-κB
  • MMPs
  • NO
  • osteoarthritis