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透辉钙长岩生物陶瓷的离子产物通过激活Wnt/β-连环蛋白信号通路诱导牙周膜细胞发生成骨分化。

The ionic products from bredigite bioceramics induced cementogenic differentiation of periodontal ligament cells via activation of the Wnt/β-catenin signalling pathway.

作者信息

Zhou Yinghong, Wu Chengtie, Zhang Xufang, Han Pingping, Xiao Yin

机构信息

Institute of Health & Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia.

出版信息

J Mater Chem B. 2013 Jul 21;1(27):3380-3389. doi: 10.1039/c3tb20445f. Epub 2013 Jun 6.

Abstract

Periodontitis results from the destructive inflammatory reaction of the host elicited by a bacterial biofilm adhering to the tooth surface and if left untreated, may lead to the loss of the teeth and the surrounding tissues, including the alveolar bone. Cementum is a specialized calcified tissue covering the tooth root and an essential part of the periodontium which enables the attachment of the periodontal ligament to the root and the surrounding alveolar bone. Periodontal ligament cells (PDLCs) represent a promising cell source for periodontal tissue engineering. Since cementogenesis is the critical event for the regeneration of periodontal tissues, this study examined whether inorganic stimuli derived from bioactive bredigite (CaMgSiO) bioceramics could stimulate the proliferation and cementogenic differentiation of PDLCs, and further investigated the involvement of the Wnt/β-catenin signalling pathway during this process via analysing gene/protein expression of PDLCs which interacted with bredigite extracts. Our results showed that the ionic products from bredigite powder extracts led to significantly enhanced proliferation and cementogenic differentiation, including mineralization-nodule formation, ALP activity and a series of bone/cementum-related gene/protein expression (ALP, OPN, OCN, BSP, CAP and CEMP1) of PDLCs in a concentration dependent manner. Furthermore, the addition of cardamonin, a Wnt/β-catenin signalling inhibitor, reduced the pro-cementogenesis effect of the bredigite extracts, indicating the involvement of the Wnt/β-catenin signalling pathway in the cementogenesis of PDLCs induced by bredigite extracts. The present study suggests that an entirely inorganic stimulus with a specific composition of bredigite bioceramics possesses the capacity to trigger the activation of the Wnt/β-catenin signalling pathway, leading to stimulated differentiation of PDLCs toward a cementogenic lineage. The results indicate the therapeutic potential of bredigite ceramics in periodontal tissue engineering application.

摘要

牙周炎是由附着在牙齿表面的细菌生物膜引发的宿主破坏性炎症反应所致,如果不加以治疗,可能会导致牙齿和周围组织(包括牙槽骨)丧失。牙骨质是覆盖牙根的一种特殊钙化组织,也是牙周组织的重要组成部分,它能使牙周韧带附着于牙根及周围的牙槽骨。牙周韧带细胞(PDLCs)是牙周组织工程中一种很有前景的细胞来源。由于牙骨质生成是牙周组织再生的关键事件,本研究检测了源自生物活性钙镁硅石(CaMgSiO)生物陶瓷的无机刺激物是否能刺激PDLCs的增殖和牙骨质生成分化,并通过分析与钙镁硅石提取物相互作用的PDLCs的基因/蛋白表达,进一步研究了Wnt/β-连环蛋白信号通路在此过程中的作用。我们的结果表明,钙镁硅石粉末提取物的离子产物以浓度依赖的方式显著增强了PDLCs的增殖和牙骨质生成分化,包括矿化结节形成、碱性磷酸酶(ALP)活性以及一系列与骨/牙骨质相关的基因/蛋白表达(ALP、骨桥蛋白(OPN)、骨钙素(OCN)、骨涎蛋白(BSP)、钙结合蛋白(CAP)和牙骨质细胞外基质蛋白1(CEMP1))。此外,添加Wnt/β-连环蛋白信号抑制剂小豆蔻明可降低钙镁硅石提取物的促牙骨质生成作用,表明Wnt/β-连环蛋白信号通路参与了钙镁硅石提取物诱导的PDLCs牙骨质生成过程。本研究表明,具有特定组成的完全无机刺激物钙镁硅石生物陶瓷具有触发Wnt/β-连环蛋白信号通路激活的能力,从而导致PDLCs向牙骨质生成谱系的分化受到刺激。这些结果表明了钙镁硅石陶瓷在牙周组织工程应用中的治疗潜力。

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