Bone formation ability of Gli1+cells in the periodontal ligament after tooth extraction

Bone formation ability of Gli1+cells in the periodontal ligament after tooth extraction
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DOI:
10.1016/j.bone.2023.116786
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发表时间:
2023-05-09
期刊:
影响因子:
4.1
通讯作者:
Hosoya,Akihiro
Hosoya,Akihiro
中科院分区:
医学2区
文献类型:
--
作者:
Fujii,Saki;Takebe,Hiroaki;Hosoya,Akihiro

文献摘要

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在拔牙后牙槽窝愈合过程中,成骨细胞在牙槽窝内出现并形成牙槽骨,但这些成骨细胞的来源仍不确定。最近,它已被证明,细胞表达Gli 1,下游因素的音刺猬信号,表现出干细胞的特性,在牙周膜(PDL)。因此,在本研究中,使用Gli 1-CreERT 2/ROSA 26-loxP-stop-loxP-tdTomato(iGli 1/Tomato)小鼠分析拔牙后Gli 1 +-PDL细胞的分化能力。在iGli 1/Tomato小鼠最后一次给予他莫昔芬后,在PDL中很少检测到Gli 1/Tomato+细胞。拔牙后一天,虽然在牙槽中出现了炎性细胞,但在牙槽骨附近仍保留了具有少量Gli 1/Tomato+细胞的Periostin+ PDL样组织。提取后三天,Gli 1/Tomato+细胞的数量增加,如窝中大量PCNA+细胞所证明的。这些Gli 1/Tomato+细胞中的一些表达BMP 4和磷酸化(P)-Smad 1/5/8。7天后,骨桥蛋白+骨基质在牙槽骨以外的牙槽中形成。Runx 2+阳性的许多Gli 1/Tomato+成骨细胞排列在新形成的骨基质表面。在Gli 1-CreERT 2/Rosa 26-loxP-stop-loxP-tdDTA(iGli 1/DTA)小鼠中不存在Gli 1 +-PDL细胞的情况下,牙槽中新形成的骨基质的量显著减少。因此,这些结果共同表明,Gli 1 +-PDL细胞分化成成骨细胞,形成骨基质的牙槽骨;因此,这种分化可能是调节,至少部分,骨形态发生蛋白(BMP)信号。
During the process of socket healing after tooth extraction, osteoblasts appear in the tooth socket and form alveolar bone; however, the source of these osteoblasts is still uncertain. Recently, it has been demonstrated that cells expressing Gli1, a downstream factor of sonic hedgehog signaling, exhibit stem cell properties in the periodontal ligament (PDL). Therefore, in the present study, the differentiation ability of Gli1+-PDL cells after tooth extraction was analyzed using Gli1-CreERT2/ROSA26-loxP-stop-loxP-tdTomato (iGli1/Tomato) mice. After the final administration of tamoxifen to iGli1/Tomato mice, Gli1/Tomato+cells were rarely detected in the PDL. One day after the tooth extraction, although inflammatory cells appeared in the tooth socket, Periostin+PDL-like tissues having a few Gli1/Tomato+cells remained near the alveolar bone. Three days after the extraction, the number of Gli1/Tomato+cells increased as evidenced by numerous PCNA+cells in the socket. Some of these Gli1/Tomato+cells expressed BMP4 and Phosphorylated (P)-Smad1/5/8. After seven days, the Osteopontin+bone matrix was formed in the tooth socket apart from the alveolar bone. Many Gli1/Tomato+osteoblasts that were positive for Runx2+were arranged on the surface of the newly formed bone matrix. In the absence of Gli1+-PDL cells in Gli1-CreERT2/Rosa26-loxP-stop-loxP-tdDTA (iGli1/DTA) mice, the amount of newly formed bone matrix was significantly reduced in the tooth socket. Therefore, these results collectively suggest that Gli1+-PDL cells differentiate into osteoblasts to form the bone matrix in the tooth socket; thus, this differentiation might be regulated, at least in part, by bone morphogenetic protein (BMP) signaling.