Regulating niche of periodontium mesenchymal stem cells under the physiological condition

生理条件下牙周组织间充质干细胞的生态位调控 牙周组织由牙骨质、牙槽骨和介于两者之间的牙周膜组成。他们的 已知生理周转是由干细胞数量支持的1，2。主要基于体外 方法：从人磨牙牙周干细胞(PDLSC)中分离出牙周干细胞(PDLSC)。尽管如此，在体内 牙周组织干细胞的定位和鉴定在很大程度上仍不清楚。 牙周炎期间或之后的牙周组织再生是一个最具挑战性的问题，尽管有各种治疗方法。 战略正在设计中。再生能力的差异强烈地表明牙周组织干细胞 在生理或病理条件下表现不同。已知干细胞的活性是 受它们所居住的利基环境的制约。各种利基信号相互作用，保持干细胞 在动态平衡中4，5。尽管其他干细胞群体的利基研究取得了巨大进展， 牙周干细胞在体内的生态位从未被研究过。 因此，要解决上述挑战，必须找出牙周组织的活体身份。 间充质干细胞(MSCs)，并了解它们的利基组织。根据我们的初步实验， Gli1+细胞被认为是成人牙周组织的间充质干细胞。Gli1+细胞被排他周围 神经血管束，在PDL间隙的顶端区域更为丰富。这些Gli1+细胞是 谱系分化阴性或典型MSC标记阴性。它们形成牙周膜、牙骨质、牙槽骨 生理性周转过程中的骨髓和根髓。阻断规范的Wnt信号导致失败 Gli1+干细胞活化和严重的牙周组织丢失。 根据这些初步发现，建议进行全面的调查，以研究体内性质 在生理条件下调节Gli1+牙周组织间充质干细胞的生态位。假设是Gli1+ MSCs是牙周组织中的主要干细胞群，受到负反馈的调节。 在牙周组织内形成环状。规范的Wnt信号通路激活和维持牙周组织间充质干细胞。 牙骨质和牙槽骨分泌的硬化素配体对Gli1+干细胞的负性调节 活动。这两个相反的信号之间的相互作用使牙周组织间充质干细胞保持动态平衡。

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.