Wnt signaling inhibits cementoblast differentiation and promotes proliferation
Wnt signaling inhibits cementoblast differentiation and promotes proliferation
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DOI：
10.1016/j.bone.2008.12.029
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发表时间：
2009-05-01
期刊：
影响因子：
4.1
通讯作者：
Shimauchi, Hidetoshi
中科院分区：
文献类型：
--
作者：
Nemoto, Eiji;Koshikawa, Yohei;Shimauchi, Hidetoshi
成牙骨质细胞，牙根衬里细胞，负责在牙根表面沉积牙骨质，这是建立功能性牙周膜不可或缺的过程。成牙骨质细胞与成骨细胞具有相同的表型特征。Wnt信号通过控制间充质干细胞或成骨细胞的功能而参与骨形成的增加;然而，Wnt信号在牙骨质形成中的作用尚未被研究。在这项研究中，我们已经确定了一个一致的表达谱Wnt信号分子在成牙骨质细胞，在体外通过RT-PCR。将细胞暴露于LiCl（其通过抑制GSK-3 β促进经典Wnt信号传导）增加β-连环蛋白核转位并上调经典Wnt响应启动子的转录活性，表明内源性经典Wnt途径在成牙骨质细胞中起作用。用LiCl激活内源性经典Wnt信号传导抑制碱性磷酸酶（ALP）活性和与牙骨质功能相关的基因的表达; ALP、骨唾液蛋白（BSP）和骨钙素（OCN）。Wnt 3a作为典型的Wnt成员，也抑制了ALP、BSP和OCN基因的表达。这种作用伴随着Runx 2和Osterix的基因表达降低以及淋巴增强因子-1的基因表达增加。Dickkopf（Dkk）-1（一种有效的经典Wnt拮抗剂，与低密度脂蛋白受体相关蛋白（LRP）-5/6共受体结合）预处理减弱了Wnt 3a对成牙骨质细胞上Runx 2和OCN mRNA表达的抑制作用。这些发现表明，经典的Wnt信号通过调节选择性转录因子的表达来抑制成牙骨质细胞的分化。Wnt 3a还增加了细胞周期蛋白D1（称为细胞周期调节因子）的表达以及细胞增殖。总之，这些观察结果表明，Wnt信号抑制成牙骨质细胞分化和促进细胞增殖。阐明Wnt在控制成牙骨质细胞功能中的作用将为改善现有牙周再生疗法提供新的工具。(C)2009 Elsevier Inc. All rights reserved.
Cementoblasts, tooth root lining cells, are responsible for laying down cementum on the root surface, a process that is indispensable for establishing a functional periodontal ligament. Cementoblasts share phenotypical features with osteoblasts. Wnt signaling has been implicated in increased bone formation by controlling mesenchymal stem cell or osteoblastic cell functions; however the role of Wnt signaling on cementogenesis has not been examined. In this study, we have identified a consistent expression profile of Wnt signaling molecules in cementoblasts, in vitro by RT-PCR. Exposure of cells to LiCl, which promotes canonical Wnt signaling by inhibiting GSK-3 beta, increased beta-catenin nuclear translocation and up-regulated the transcriptional activity of a canonical Wnt-responsive promoters, suggesting that an endogenous canonical Wnt pathway functions in cementoblasts. Activation of endogenous canonical Wnt signaling with LiCl suppressed alkaline phosphatase (ALP) activity and expression of genes associated with cementum function; ALP, bone sialoprotein (BSP), and osteocalcin (OCN). Exposure to Wnt3a, as a representative canonical Wnt member, also inhibited the expression of ALP, BSP, and OCN gene. This effect was accompanied by decreased gene expression of Runx2 and Osterix and by increased gene expression of lymphoid enhancer factor-1. Pretreatment with Dickkopf (Dkk)-1, a potent canonical Wnt antagonist, which binds to a low-density lipoprotein-receptor-related protein (LRP)-5/6 co-receptor, attenuated the suppressive effects of Wnt3a on mRNA expression of Runx2 and OCN on cementoblasts. These findings suggest that canonical Wnt signaling inhibits cementoblast differentiation via regulation of expression of selective transcription factors. Wnt3a also increased the expression of cyclin D1, known as a cell cycle regulator, as well as cell proliferation. In conclusion, these observations suggest that Wnt signaling inhibits cementoblast differentiation and promotes cell proliferation. Elucidating the role of Wnt in controlling cementoblast function will provide new tools needed to improve on existing periodontal regeneration therapies. (C) 2009 Elsevier Inc. All rights reserved.