Dissecting specific Wnt components governing osteogenic differentiation potential by human periodontal ligament stem cells through interleukin-6.
Dissecting specific Wnt components governing osteogenic differentiation potential by human periodontal ligament stem cells through interleukin-6.
复制标题
通过白细胞介素-6解剖控制人牙周韧带干细胞成骨分化潜能的特定Wnt成分。
DOI：
10.1038/s41598-023-35569-8
复制
发表时间：
2023-06-03
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
牙周韧带干细胞（Periodontal ligament stem cells, PDLSCs）在牙周组织和牙槽骨稳态中起着重要作用。在炎症过程中，白细胞介素(IL)-6是控制组织反应和牙槽骨组织重塑的关键细胞因子之一。人们认为牙周组织炎症会导致牙周组织降解，尤其是牙槽骨。然而，在这项研究中，我们发现炎症介质IL-6可能在炎症状态下对牙槽骨稳态起另一个方向的作用。我们发现，IL-6在10和20 ng/mL时没有细胞毒性，并且剂量依赖性地对人PDLSCs （hPDLSCs）的成骨分化产生有益作用，这可以通过增加碱性磷酸酶活性、成骨标志物mRNA表达和基质矿化来证明。在生理和炎症水平IL-6存在的情况下，hPDLSCs的成骨分化潜能通过多种可能的机制增强，包括转化生长因子（TGF）、Wnt和Notch通路。经过深入深入的探索，我们发现在IL-6呈现的情况下，Wnt通路是hPDLSCs成骨分化的关键调控因子。令人惊讶的是，除了其他间充质干细胞外，hPDLSCs使用不同的Wnt成分，并且典型和非典型Wnt通路由不同的机制触发。通过基因沉默、重组Wnt配体处理和β-catenin稳定/易位进一步验证，证实IL-6通过WNT2B或WNT10B调控典型Wnt/β-catenin通路，并利用WNT5A激活非典型Wnt通路。这些发现证实了控制牙周组织和牙槽骨再生的稳态途径，并可能为进一步修复组织的治疗方案设计提供依据。
Periodontal ligament stem cells (PDLSCs) play a significant role on periodontal tissue and alveolar bone homeostasis. During inflammation, interleukin (IL)-6 serves as one of key cytokine players controlling tissue reaction as well as alveolar bone tissue remodeling. It is believed that periodontal tissue inflammation causes periodontium degradation, especially alveolar bone. However, in this study, we show that an inflammatory mediator, IL-6, may serve another direction on alveolar bone homeostasis during inflammatory condition. We found that, IL-6 at 10 and 20 ng/mL was not cytotoxic and dose-dependently exerted beneficial effects on osteogenic differentiation of human PDLSCs (hPDLSCs), as demonstrated by increased alkaline phosphatase activity, mRNA expression of osteogenic markers, and matrix mineralization. The presence of physiological and inflammatory level of IL-6, the osteogenic differentiation potential by hPDLSCs was enhanced by several possible mechanisms including transforming growth factor (TGF), Wnt, and Notch pathways. After in-depth and thorough exploration, we found that Wnt pathway serves as key regulator controlling osteogenic differentiation by hPDLSCs amid the IL-6 presentation. Surprisingly, apart from other mesenchymal stem cells, distinct Wnt components are employed by hPDLSCs, and both canonical and non-canonical Wnt pathways are triggered by different mechanisms. Further validation by gene silencing, treatment with recombinant Wnt ligands, and β-catenin stabilization/translocation confirmed that IL-6 governed the canonical Wnt/β-catenin pathway via either WNT2B or WNT10B and employed WNT5A to activate the non-canonical Wnt pathway. These findings fulfill the homeostasis pathway governing periodontal tissue and alveolar bone regeneration and may serve for further therapeutic regimen design for restoring the tissues.
登录
查看更多内容
DOI：
10.1155/2011/765624
发表时间：
2011
期刊：
Arthritis
影响因子：
--
作者：
Hashizume M;Mihara M
通讯作者：
Mihara M
影响因子：
4.4
作者：
Hirano T
通讯作者：
Hirano T
影响因子：
5.2
作者：
How KY;Song KP;Chan KG
通讯作者：
Chan KG
影响因子：
4.8
作者：
Gilbert, L;He, XF;Nanes, MS
通讯作者：
Nanes, MS
人脂肪衍生的干细胞（HASC）的成骨潜力，属于小梁钛脊柱笼子。
影响因子：
4.6
作者：
Caliogna L;Bina V;Botta L;Benazzo FM;Medetti M;Maestretti G;Mosconi M;Cofano F;Tartara F;Gastaldi G
通讯作者：
Gastaldi G