Ameloblastin in Hertwig's epithelial root sheath regulates tooth root formation and development.
Ameloblastin in Hertwig's epithelial root sheath regulates tooth root formation and development.
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DOI：
10.1371/journal.pone.0054449
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Tanne K
中科院分区：
文献类型：
--
作者：
Hirose N;Shimazu A;Watanabe M;Tanimoto K;Koyota S;Sugiyama T;Uchida T;Tanne K
牙根的形成是在牙冠形态发生完成后开始的。在牙冠的端缘，内、外釉上皮形成Hertwig上皮根鞘（HERS）。HERS沿着牙囊组织延伸，用于牙根形成。成釉蛋白（Ameloblastin，AMBN）是由成釉细胞和HERS衍生细胞分泌的釉基质蛋白。除了AMBN外，许多釉质蛋白在牙根形成中被消除。AMBN可能与牙根形成有关;然而，其在此过程中的作用尚不清楚。在本研究中，我们发现AMBN在小鼠的下第一磨牙的HERS的基底部分，而不是在尖端。我们根据小鼠AMBN基因序列设计并合成了靶向AMBN的小干扰RNA（siRNA）。当AMBN siRNA注射到出生后10天的小鼠的预期下颌第一磨牙中时，10天后牙根变短。HERS呈多层结构，5-溴-2 ′-脱氧尿苷（5-bromo-2′-deoxyuridine，BrdU）阳性细胞在外层增多。在体外实验中，当细胞与瞬时表达和不表达AMBN mRNA相比，生长抑制基因，如p21 Cip 1和p27 Kip 1的表达增强，而AMBN和BrdU掺入增加。因此，AMBN可调节HERS衍生细胞的分化状态。此外，我们的研究结果表明，表达AMBN在HERS的功能作为一个触发正常的根形成。
Tooth root formation begins after the completion of crown morphogenesis. At the end edge of the tooth crown, inner and outer enamel epithelia form Hertwig’s epithelial root sheath (HERS). HERS extends along with dental follicular tissue for root formation. Ameloblastin (AMBN) is an enamel matrix protein secreted by ameloblasts and HERS derived cells. A number of enamel proteins are eliminated in root formation, except for AMBN. AMBN may be related to tooth root formation; however, its role in this process remains unclear. In this study, we found AMBN in the basal portion of HERS of lower first molar in mice, but not at the tip. We designed and synthesized small interfering RNA (siRNA) targeting AMBN based on the mouse sequence. When AMBN siRNA was injected into a prospective mandibular first molar of postnatal day 10 mice, the root became shorter 10 days later. Furthermore, HERS in these mice revealed a multilayered appearance and 5-bromo-2′-deoxyuridine (BrdU) positive cells increased in the outer layers. In vitro experiments, when cells were compared with and without transiently expressing AMBN mRNA, expression of growth suppressor genes such as p21Cip1 and p27Kip1 was enhanced without AMBN and BrdU incorporation increased. Thus, AMBN may regulate differentiation state of HERS derived cells. Moreover, our results suggest that the expression of AMBN in HERS functions as a trigger for normal root formation.
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DOI：
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发表时间：
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期刊：
Molecular therapy. Nucleic acids
影响因子：
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