GRP78 promotes the osteogenic and angiogenic response in periodontal ligament stem cells.
GRP78 promotes the osteogenic and angiogenic response in periodontal ligament stem cells.
复制标题
GRP78促进牙周韧带干细胞成骨和血管生成反应。
DOI：
10.22203/ecm.v045a02
复制
发表时间：
2023-01-23
影响因子：
3.1
通讯作者：
中科院分区：
文献类型：
--
作者：
牙周炎是一种渐进性疾病，最终导致骨骼和牙齿脱落。牙周病的一个主要后果是无法重新获得牙周组织中丢失的骨。葡萄糖调节蛋白78（glucose-regulated protein-78，GRP 78）在牙周膜干细胞的成骨分化中的重要性及其在牙周组织再生中的潜在应用已被证实。以往的研究表明GRP 78与牙本质基质蛋白1（dentine matrix protein-1，DMP 1）之间存在一定的关系。本研究证实了这种受体-配体复合物在支持骨生成和血管生成过程中的重要性。为了显示GRP 78在矿化组织中的功能，产生了转基因牙周膜干细胞（PDLSC），其中GRP 78过表达或沉默。在成骨条件下培养的细胞的基因表达分析显示，随着GRP 78的过表达，关键成骨基因增加。还进行了RNA-Seq分析以了解与基因型变化相关的转录组谱。使用注释、可视化和整合发现数据库（大卫）进行差异表达基因的功能富集分析，证实了GRP 78过表达促进骨生成和血管生成的基因的上调。茜素红染色和扫描电子显微镜分析显示基质矿化与增加钙沉积在GRP 78过表达细胞。使用皮下植入啮齿动物模型显示GRP 78的体内成骨和血管生成功能。结果表明，GRP 78在PDLSCs中的表达可以调节成骨和血管生成。因此，GRP 78可作为牙周病修复的治疗靶点。本文的评审员没有提出任何问题;因此，没有与评审员讨论部分。负责这篇论文的科学编辑是Thimios Mitsiadis。
Periodontitis is a progressive disease that ultimately leads to bone and tooth loss. A major consequence of periodontal disease is the inability to regain lost bone in the periodontium. The importance was demonstrated of glucose-regulated protein-78 (GRP78) in the osteogenic differentiation of periodontal ligament stem cells and their potential use for regeneration of the periodontium. Previous studies have shown the relationship between GRP78 and dentine matrix protein-1 (DMP1). The importance of this receptor-ligand complex in supporting the process of osteogenesis and angiogenesis was confirmed in this study. To show the function of GRP78 in mineralised tissues, transgenic periodontal ligament stem cells (PDLSCs) were generated in which GRP78 was either overexpressed or silenced. Gene expression analysis of the cells cultured under osteogenic conditions showed an increase in key osteogenic genes with the overexpression of GRP78. RNA-Seq analysis was also performed to understand the transcriptome profile associated with genotype changes. Using the database for annotation, visualisation, and integration discovery (DAVID) for the functional enrichment analysis of differentially expressed genes, the upregulation of genes promoting osteogenesis and angiogenesis with GRP78 overexpression was demonstrated. Alizarin red staining and scanning electron microscopy analysis revealed matrix mineralisation with increased calcium deposition in GRP78 overexpressing cells. The in vivo osteogenic and angiogenic function of GRP78 was shown using a subcutaneous implantation rodent model. The results suggested that GRP78 in PDLSCs can regulate the expression of both osteogenesis and angiogenesis. Therefore, GRP78 could be considered as a therapeutic target for repair of diseased periodontium. There were no questions from reviewers for this paper; therefore, there is no Discussion with reviewers section. The Scientific Editor responsible for this paper was Thimios Mitsiadis.