Gli1+-PDL Cells Contribute to Alveolar Bone Homeostasis and Regeneration
Gli1+-PDL Cells Contribute to Alveolar Bone Homeostasis and Regeneration
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DOI：
10.1177/00220345221106921
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发表时间：
2022-07-04
影响因子：
7.6
通讯作者：
Hosoya, A.
中科院分区：
文献类型：
--
作者：
Shalehin, N.;Seki, Y.;Hosoya, A.
牙周膜(PDL)含有间充质干细胞(MSCs)，可分化为成骨细胞、成牙骨质细胞和成纤维细胞。然而，这些细胞的分布和特征仍然不确定。Gli1是一种必需的刺猬信号转录因子，在胚胎发育过程中作用于未分化的细胞。因此，本研究利用Gli1-CreERT2/rosa26-loxP-Stop-loxP-tdTomato(iGli1/Tomato)小鼠检测Gli1(+)细胞的分化能力。在4周龄的iGli1/Tomato小鼠中，仅在表达内粘蛋白的血管周围的PDL中检测到Gli1/Tomato(+)细胞。随着时间的推移，这些细胞已经增殖，在第28天定位于PDL以及骨和牙骨质表面。然而，在8周龄的iGli1/Tomato小鼠中，Gli1/Tomato(+)细胞处于静止状态，因为大多数细胞对Ki-67没有免疫反应。这些细胞在8周龄的小鼠身上表现出高的集落形成单位成纤维细胞活性，并能够在体外分化为成骨、成软骨和成脂。此外，将iGli1/Tomato小鼠的牙齿移植到野生型小鼠的皮下后，在再生骨的成骨细胞和骨细胞中检测到番茄荧光，表明Gli1(+)细胞的后代。结果表明，牙周膜细胞中的Gli1(+)细胞为间充质干细胞，对牙槽骨再生有一定的促进作用。
The periodontal ligament (PDL) contains mesenchymal stem cells (MSCs) that can differentiate into osteoblasts, cementoblasts, and fibroblasts. Nevertheless, the distribution and characteristics of these cells remain uncertain. Gli1, an essential hedgehog signaling transcription factor, functions in undifferentiated cells during embryogenesis. Therefore, in the present study, the differentiation ability of Gli1(+) cells was examined using Gli1-CreERT2/ROSA26-loxP-stop-loxP-tdTomato (iGli1/Tomato) mice. In 4-wk-old iGli1/Tomato mice, Gli1/Tomato(+) cells were only slightly detected in the PDL, around endomucin-expressing blood vessels. These cells had proliferated over time, localizing in the PDL as well as on the bone and cementum surfaces at day 28. However, in 8-wk-old iGli1/Tomato mice, Gli1/Tomato(+) cells were quiescent, as most cells were not immunoreactive for Ki-67. These cells in 8-wk-old mice exhibited high colony-forming unit fibroblast activity and were capable of osteogenic, chondrogenic, and adipogenic differentiation in vitro. In addition, after transplantation of teeth of iGli1/Tomato mice into the hypodermis of wild-type mice, Tomato fluorescence indicating the progeny of Gli1(+) cells was detected in the osteoblasts and osteocytes of the regenerated bone. These results demonstrate that Gli1(+) cells in the PDL were MSCs and could contribute to the alveolar bone regeneration.