Expression of the Hutchinson-Gilford Progeria Mutation Leads to Aberrant Dentin Formation.
Expression of the Hutchinson-Gilford Progeria Mutation Leads to Aberrant Dentin Formation.
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DOI：
10.1038/s41598-018-33764-6
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发表时间：
2018-10-18
影响因子：
4.6
通讯作者：
Cho ES
中科院分区：
文献类型：
--
作者：
Choi H;Kim TH;Jeong JK;Strandgren C;Eriksson M;Cho ES
Hutchinson-Gilford progeria syndrome (HGPS) is a rare accelerated senescence disease, manifesting dental abnormalities and several symptoms suggestive of premature aging. Although irregular secondary dentin formation in HGPS patients has been reported, pathological mechanisms underlying aberrant dentin formation remain undefined. In this study, we analyzed the mandibular molars of a tissue-specific mouse model that overexpresses the most common HGPS mutation (LMNA, c.1824C > T, p.G608G) in odontoblasts. In the molars of HGPS mutant mice at postnatal week 13, targeted expression of the HGPS mutation in odontoblasts results in excessive dentin formation and pulp obliteration. Circumpulpal dentin of HGPS mutants was clearly distinguished from secondary dentin of wild-type (WT) littermates and its mantle dentin by considering the irregular porous structure and loss of dentinal tubules. However, the dentin was significantly thinner in the molars of HGPS mutants at postnatal weeks 3 and 5 than in those of WT mice. In vitro analyses using MDPC-23, a mouse odontoblastic cell line, showed cellular senescence, defects of signaling pathways and consequential downregulation of matrix protein expression in progerin-expressing odontoblasts. These results indicate that expression of the HGPS mutation in odontoblasts disturbs physiological secondary dentin formation. In addition, progerin-expressing odontoblasts secrete paracrine factors that can stimulate odontogenic differentiation of dental pulp cells. Taken together, our results suggest that the aberrant circumpulpal dentin of HGPS mutants results from defects in physiological secondary dentin formation and consequential pathologic response stimulated by paracrine factors from neighboring progerin-expressing odontoblasts.
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影响因子：
2.6
作者：
Oka, Shoji;Oka, Kyoko;Chai, Yang
通讯作者：
Chai, Yang
基因组不稳定性和前后A中的DNA损伤反应。
DOI：
10.18632/aging.100012
发表时间：
2009-01
期刊：
Aging
影响因子：
--
作者：
Musich PR;Zou Y
通讯作者：
Zou Y
影响因子：
4.1
作者：
Gluhak-Heinrich, J.;Guo, D.;Yang, W.;Harris, M. A.;Lichtler, A.;Kream, B.;Zhang, J.;Feng, J. Q.;Smith, L. C.;Dechow, P.;Harris, S. E.
通讯作者：
Harris, S. E.
DOI：
10.18632/aging.100717
发表时间：
2015-01
期刊：
Aging
影响因子：
--
作者：
Aliper AM;Csoka AB;Buzdin A;Jetka T;Roumiantsev S;Moskalev A;Zhavoronkov A
通讯作者：
Zhavoronkov A
DOI：
10.1073/pnas.192460799
发表时间：
2002-10-01
影响因子：
11.1
作者：
Bergo, MO;Gavino, B;Young, SG
通讯作者：
Young, SG