Wnt/β-catenin pathway regulates cementogenic differentiation of adipose tissue-deprived stem cells in dental follicle cell-conditioned medium.
Wnt/β-catenin pathway regulates cementogenic differentiation of adipose tissue-deprived stem cells in dental follicle cell-conditioned medium.
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DOI：
10.1371/journal.pone.0093364
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Deng M
中科院分区：
文献类型：
--
作者：
Liu N;Gu B;Liu N;Nie X;Zhang B;Zhou X;Deng M
新牙骨质的形成和附着是牙周组织再生的关键。组织工程是目前探索实现完整的，可靠的和可再生的牙周组织再生。多能性和自我更新能力使脂肪组织剥夺干细胞（ADSCs）成为组织再生和修复的优秀细胞来源。大鼠ADSC在添加Wnt通路抑制剂DKK-1的牙囊细胞条件培养基（DFC-CM）中培养7天后，表现出成牙骨质细胞谱系的几种表型特征，如CAP、ALP、BSP和OPN mRNA表达水平上调，BSP和CAP蛋白表达加速。Wnt/β-catenin信号通路通过调节靶基因的表达来控制干细胞的分化。成牙骨质细胞与成骨细胞具有相同的表型特征。在这项研究中，我们证明了在补充有DKK-1的DFC-CM中培养ADSC导致β-catenin核转位的抑制，并下调TCF-4和LEF-1 mRNA的表达水平。我们还发现DKK-1可以促进ADSCs向牙骨质分化，这一点通过上调CAP、ALP、BSP和OPN基因的表达而得到证实。另一方面，在补充有100 ng/mL Wnt 3a（其激活Wnt/β-连环蛋白途径）的DFC-CM中培养ADSC消除了这种作用。总而言之，我们的研究表明Wnt/β-catenin信号通路在调节DFC-CM中培养的ADSC的牙骨质分化中发挥着重要作用。这些结果提高了通过修饰Wnt/β-catenin途径使用ADSCs进行牙周再生的可能性。
The formation and attachment of new cementum is crucial for periodontium regeneration. Tissue engineering is currently explored to achieve complete, reliable and reproducible regeneration of the periodontium. The capacity of multipotency and self-renewal makes adipose tissue-deprived stem cells (ADSCs) an excellent cell source for tissue regeneration and repair. After rat ADSCs were cultured in dental follicle cell-conditioned medium (DFC-CM) supplemented with DKK-1, an inhibitor of the Wnt pathway, followed by 7 days of induction, they exhibited several phenotypic characteristics of cementoblast lineages, as indicated by upregulated expression levels of CAP, ALP, BSP and OPN mRNA, and accelerated expression of BSP and CAP proteins. The Wnt/β-catenin signaling pathway controls differentiation of stem cells by regulating the expression of target genes. Cementoblasts share phenotypical features with osteoblasts. In this study, we demonstrated that culturing ADSCs in DFC-CM supplemented with DKK-1 results in inhibition of β-catenin nuclear translocation and down-regulates TCF-4 and LEF-1 mRNA expression levels. We also found that DKK-1 could promote cementogenic differentiation of ADSCs, which was evident by the up-regulation of CAP, ALP, BSP and OPN gene expressions. On the other hand, culturing ADSCs in DFC-CM supplemented with 100 ng/mL Wnt3a, which activates the Wnt/β-catenin pathway, abrogated this effect. Taken together, our study indicates that the Wnt/β-catenin signaling pathway plays an important role in regulating cementogenic differentiation of ADSCs cultured in DFC-CM. These results raise the possibility of using ADSCs for periodontal regeneration by modifying the Wnt/β-catenin pathway.
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影响因子：
15.8
作者：
Chen Y;Whetstone HC;Lin AC;Nadesan P;Wei Q;Poon R;Alman BA
通讯作者：
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DOI：
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