Regulating niche of periodontium mesenchymal stem cells under the physiological condition

生理条件下牙周间充质干细胞生态位的调节

• 批准号: 10335269
• 负责人: JIAN Q. FENG
• 金额: --
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-01 至 2022-05-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10335269
• 关键词: Ablation; Address; Adult; Apical; Apoptosis; Cells; Dental Cementum; Dental Pulp; Equilibrium; Failure; Feedback; Foundations; Future; Human; In Vitro; Investigation; LacZ Genes; Learning; Ligands; Location; Maintenance; Mesenchymal Stem Cells; Modeling; Mus; Natural regeneration; Pathologic; Pathway interactions; Periodontal Ligament; Periodontitis; Periodontium; Physiological; Plant Roots; Property; Regulation; Research; Role; Signal Transduction; Testing; Tissues; Tooth structure; Transgenic Mice; Transgenic Organisms; WNT Signaling Pathway; alveolar bone; base; design; experimental study; in vivo; injury and repair; mouse model; neurovascular; novel strategies; regenerative therapy; stem cell biomarkers; stem cell niche; stem cell population; stem cells; tissue injury; treatment strategy

Regulating niche of periodontium mesenchymal stem cells under the physiological condition The periodontium is composed of cementum, alveolar bone and periodontal ligament (PDL) in between. Their physiological turnover was known to be supported by stem cell populations1, 2. Based on mostly in vitro approaches, the periodontal stem cells (PDLSC) were isolated from human molar PDL3. Despite of that, in vivo location and identification of the periodontium stem cells remain largely unknown. Periodontium regeneration during or after periodontitis is a most challenging issue despite of various treatment strategies being designed. The regeneration capability difference strongly suggests that periodontium stem cells behave differentially under physiological or pathological conditions. Activity of stem cells was known to be regulated by the niche they are residing in. Various niche signals interplay which each other and keep stem cells in a dynamic balance4, 5. Despite of tremendous progress of the niche studies for other stem cell populations, the in vivo niche of periodontium stem cells has never been studied. To address above challenges, it is therefore imperative to find out the in vivo identity of the periodontium mesenchymal stem cells (MSCs) and to learn their niche organization. Based on our preliminary experiments, Gli1+ cells are identified as the MSCs for adult periodontium tissue. The Gli1+ cells are exclusively surrounding the neurovascular bundle and are more enriched in the apical region of the PDL space. These Gli1+ cells are negative for lineage differentiation or classical MSC markers. They give rise to the PDL, cementum, alveolar bone and apical root pulp during physiological turnover. Blockage of canonical Wnt signaling leads to failure of Gli1+ stem cells activation and severe periodontal tissue loss. With these preliminary findings, comprehensive investigation is proposed for investigating the in vivo properties and regulating niche of Gli1+ periodontium MSCs under physiological condition. The hypothesis is that Gli1+ MSCs are the dominant stem cell population within the periodontium and are regulated by a negative feedback loop within the periodontium. Canonical Wnt signaling pathway activates and maintains periodontium MSCs. Sclerostin ligand secreted from the cementum and alveolar bone negatively regulates the Gli1+ stem cell activities. Interplays between the two opposing signals keep the periodontium MSCs in a dynamic balance.

在生理条件下调节牙周间充质干细胞的小境 该牙周由牙髓，牙槽骨和牙周韧带（PDL）组成。他们的 已知生理周转率得到了干细胞种群的支持1，2。主要基于体外 方法是，从人摩尔PDL3中分离出牙周干细胞（PDLSC）。尽管如此，体内 牙周干细胞的位置和鉴定在很大程度上未知。 牙周炎期间或牙周炎后的牙周再生是最具挑战性的问题 设计策略。再生能力差异强烈表明牙周干细胞 在生理或病理条件下的行为差异。已知干细胞的活性是 由他们所居住的利基市场调节。各种利基信号相互作用，彼此保持干细胞 在动态平衡中4，5。尽管利基研究在其他干细胞种群中取得了巨大进展 从未研究过牙周干细胞的体内生态位。 为了应对上述挑战，因此必须找出牙周的体内身份 间充质干细胞（MSC）并学习其利基组织。根据我们的初步实验， Gli1+细胞被鉴定为成人牙周组织的MSC。 Gli1+细胞完全围绕 神经血管束，更丰富在PDL空间的顶端区域。这些Gli1+细胞是 谱系分化或经典MSC标记为负。它们产生PDL，牙骨质，肺泡 生理周转期间的骨头和顶根纸浆。构成Wnt信号的阻塞导致失败 GLI1+干细胞激活和严重的牙周组织丧失。 通过这些初步发现，提出了全面研究用于研究体内特性 并在生理条件下调节GLI1+牙周MSC的利基市场。假设是Gli1+ MSC是牙周内的主要干细胞种群，受负反馈的调节 牙周内循环。典型的Wnt信号通路会激活并维持牙周MSC。 硬化蛋白配体从牙骨质分泌，肺泡骨负调节Gli1+干细胞 活动。两个相对信号之间的相互作用使牙周MSC保持动态平衡。