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S100A4 upregulation suppresses tissue ossification and enhances matrix degradation in experimental periodontitis models
  • ISSN号:1671-4083
  • 期刊名称:《中国药理学报:英文版》
  • 分类:Q516[生物学—生物化学] TQ658.41[化学工程—精细化工]
  • 作者机构:[1]Shanghai Engineering Research Center of Tooth Restoration and Regeneration, School of Stomatology, Tongji University, Shanghai 200072, China, [2]Shanghai East Hospital, The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine, Tongji University, Shanghai 200092, China
  • 相关基金:Acknowledgements This work was funded by the Chinese National Science Technology Support Program (grant No 2014BAI04B07), the National Natural Science Foundation of China (grant No 81271110), the Fundamental Research Funds for the Central Universities (No1504219037) and the Shanghai Health Bureau Youth Research Project (grant No 552012). We thank Prof Huan-xin MENG (Peking University), Prof Yao SUN and Dr De-tao WANG (Shanghai University) for their substantial help with this research.
中文摘要:

目的: S100A4,也已知的同样成纤维细胞特定的蛋白质 1 或 metastasin 1,不仅高度在刺激生长的有教养的房间和变形肿瘤房间,而且在牙齿周围的系带表示了。这研究的目的是在煽动性的 milieu.Methods 在 periodontitis 和它的规章的机制的致病调查 S100A4 的角色: 试验性的 periodontitis 被亚缘的丝绸绑扎在老鼠导致。在牙齿周围的系带的陷井活动和 S100A4 表示用 immunohistochemistry 和 immunofluorescence 方法被检验。IL-1β;对待的人的牙齿周围的系带房间(hPDLCs ) 被用作在试验性的 periodontitis 的 vitro 模型。S100A4 mRNA 和蛋白质分别地用 qRT-PCR 和西方的污点被估计。hPDLCs 是有任何一个 S100A4 overexpression plasmids 或 shRNAs plasmids 的 transfected。在 hPDLCs 的矿化作用与 12-d osteogenic 正式就职试金被评估,并且高山, OCN , MMP-2 和 MMP-13 的表示被 qRT-PCR.Results 分析:在有试验性的 periodontitis 的老鼠的牙齿周围的系带,陷井活动和 S100A4 蛋白质染色与在控制老鼠的那些相比是更加更强烈的。有 IL-1β 的 hPDLCs 的处理;(10, 50 和 100 ng/mL ) dose-dependently 增加了 mRNA 和 S100A4 的蛋白质层次。有 shRNAs 的 Transfection 显著地在 hPDLCs 增加了使矿物化的小瘤形成和osteogenic相关的标记高山和 OCN 层次,而 S100A4 的 overexpression 显著地减少了使矿物化的小瘤形成,并且在 hPDLCs.Conclusion 增加了矩阵降级酶 MMP-2 和 MMP-13 层次: S100A4 是在试验性的老鼠 periodontitis 并且在 IL-1β 的 upregulated ;对待的 hPDLCs ,在 S100A4 压制 osteogenic 区别并且提高矩阵降级的地方。因此, S100A4 是为 periodontitis 的处理的一个潜在的目标。

英文摘要:

Aim: S100A4, also known as fibroblast-specific protein I or metastasin 1, is not only highly expressed in growth-stimulated cultured cells and metastatic tumor cells, but also in the periodontal ligament. The aim of this study was to investigate the roles of SlOOA4 in the pathogenesis of periodontitis and its regulatory mechanisms in inflammatory milieu. Methods: Experimental periodontitis was induced in rats by submarginal silk ligatures. TRAP activity and S100A4 expression in periodontal ligaments were examined using immunohistochemistry and immunofluorescence methods. IL-1β-treated human periodontal ligament cells (hPDLCs) were used as in vitro model of experimental periodontitis. S100A4 mRNA and protein were assessed using qRT-PCR and Western blot, respectively, hPDLCs were transfected with either S100A4 overexpression plasmids or shRNAs plasmids. The mineralization in hPDLCs was evaluated with a 12-d osteogenic induction assay, and the expression of ALP, OCN, MMP-2 and MMP-13 was analyzed by qRT-PCR. Results: In the periodontal ligaments of rats with experimental periodontitis, TRAP activity and SlOOA4 protein staining were considerably more intense compared with those in the control rats. Treatment of hPDLCs with IL-1β (10, 50 and 100 ng/mL) dose- dependently increased the mRNA and protein levels of S100A4. Transfection with shRNAs markedly increased mineralized nodule formation and the osteogenic-related markers ALP and OCN levels in hPDLCs, whereas the overexpression of S100A4 significantly reduced mineralized nodule formation, and increased the matrix degradation enzymes MMP-2 and MMP-13 levels in hPDLCs. Conclusion: S100A4 is upregulated in the experimental rat periodontitis and in IL-1β-treated hPDLCs, where S100A4 suppresses osteogenic differentiation and enhances matrix degradation. Thus, S100A4 is a potential target for the treatment of periodontitis.

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期刊信息
  • 《中国药理学报:英文版》
  • 中国科技核心期刊
  • 主管单位:中国科学技术协会
  • 主办单位:中科院上海药物研究所
  • 主编:丁光生
  • 地址:上海市太原路294号31号楼
  • 邮编:200031
  • 邮箱:
  • 电话:021-54922821 54922822
  • 国际标准刊号:ISSN:1671-4083
  • 国内统一刊号:ISSN:31-1347/R
  • 邮发代号:4-295
  • 获奖情况:
  • 1992、1996年两届全国优秀科技期刊一等奖,1992、1996、1997年中国科协、中科院以及上海市优...,首届国家期刊奖、2000年中科院优秀期刊评比特别奖
  • 国内外数据库收录:
  • 俄罗斯文摘杂志,美国化学文摘(网络版),英国农业与生物科学研究中心文摘,波兰哥白尼索引,荷兰文摘与引文数据库,荷兰医学文摘,美国生物医学检索系统,美国剑桥科学文摘,美国科学引文索引(扩展库),美国生物科学数据库,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,英国食品科技文摘,中国北大核心期刊(2000版)
  • 被引量:1239