The Sirt6 gene: Does it play a role in tooth development?
The Sirt6 gene: Does it play a role in tooth development?
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Sirt6 基因：它在牙齿发育中发挥作用吗？
DOI：
10.1371/journal.pone.0174255
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Ye L
中科院分区：
文献类型：
--
作者：
Liao X;Feng B;Zhang D;Liu P;Zhou X;Li R;Ye L
牙齿间充质细胞(DMC)在牙齿发育以及牙齿组织的修复和再生中起重要作用。大量的信号分子调控DMC的增殖和分化，但其潜在的机制仍不完全清楚。SIRT6(sirtuin-6，SIRT6)是衰老的关键调节因子，对胚胎干细胞(ESC)的分化有影响。小鼠骨髓细胞中SIRT6基因的实验性缺失已被发现对这些细胞的骨密度和成骨分化具有抑制作用。然而，SIRT6在牙齿发育中的可能作用目前仍在很大程度上尚不清楚。在本研究中，我们发现SIRT6对出生前的牙齿发育没有影响。然而，基因敲除小鼠的SIRT6基因缺失确实有两个出生后的影响：牙齿萌出延迟和牙根发育迟缓。我们建议解释在SIRT6-/-小鼠中观察到的变化的可能的分子基础。SIRT6在小鼠成牙本质细胞中表达。SIRT6基因缺失增强了骨髓间充质干细胞的增殖和成脂分化能力。另一方面，它抑制了它们在体外的成骨/成软骨分化能力。进一步的研究表明，SIRT6在牙齿发育中的作用可能与其他因素有关。其中包括核因子-κB、p38丝裂原活化蛋白激酶、细胞外调节的丝裂原活化蛋白激酶通路和线粒体能量。我们证实了SIRT6在牙根形成中的作用，并证实SIRT6对于DMC的分化以及牙根的发育和最终的牙萌出都是必需的。这些结果建立了SIRT6和牙齿发育之间的新联系。
Dental Mesenchymal Cells (DMCs) are known to play a role in tooth development as well as in the repair and regeneration of dental tissue. A large number of signaling molecules regulate the proliferation and differentiation of DMC, though the underlying mechanisms are still not fully understood. Sirtuin-6 (SIRT6), a key regulator of aging, can exert an impact on embryonic stem cell (ESC) differentiation. The experimental deletion of Sirt6 in mouse bone marrow cells has been found to have an inhibiting impact on the bone mineral density and the osteogenic differentiation of these cells. The possible role of Sirt6 in tooth development, however, has at present remained largely unexplored. In the present study, we found that SIRT6 had no effect on tooth development before birth. However, Sirt6 gene deletion in knockout mice did have two post-natal impacts: a delay in tooth eruption and sluggishness in the development of dental roots. We propose an explanation of the possible molecular basis of the changes observed in Sirt6-/- mice. SIRT6 is expressed in mouse odontoblasts. Sirt6 deletion enhanced the proliferation of DMCs, as well as their capacity for adipogenic differentiation. On the other hand, it inhibited their capacity for in vitro osteogenic/chondrogenic differentiation. Further studies suggested that other factors may mediate the role of Sirt6 in odontogenesis. These include the nuclear factor kappa B (NF-κB), p38 mitogen-activated protein kinase (p38-MAPK), extracellular regulated MAP kinase (ERK) pathways and the mitochondrial energy. We demonstrated that Sirt6 plays a role in tooth root formation and confirmed that SIRT6 is necessary for DMC differentiation as well as for the development of the tooth root and for eventual tooth eruption. These results establish a new link between SIRT6 and tooth development.