MiR-17 Modulates Osteogenic Differentiation Through a Coherent Feed-Forward Loop in Mesenchymal Stem Cells Isolated from Periodontal Ligaments of Patients with Periodontitis

作者：Yali Liu, Wenjia Liu, Cheng‐Hu Hu, Zengfu Xue, Guang Wang, Bofu Ding, Hailang Luo, Liang Tang, Xiangwei Kong, Xiaoyan Chen, Na Liu, Yin Ding, Yan Jin · 发表于：Stem Cells · 年份：2011 · DOI：10.1002/stem.728 · 被引用次数：174 · 研究领域：Mesenchymal stem cell research、Periodontal Regeneration and Treatments、dental development and anomalies

Chronic inflammatory diseases, such as rheumatoid arthritis and periodontitis, are the most common causes of bone tissue destruction. Recently, human periodontal ligament tissue-derived mesenchymal stem cells (PDLSCs), a population of multipotent stem cells, have been used to reconstruct tissues destroyed by chronic inflammation. However, the impact of the local inflammatory microenvironment on tissue-specific stem cells and the mechanisms controlling the effects of the local inflammatory environment remain poorly understood. In this study, we found that the multidifferentiation potential of mesenchymal stem cells (MSCs) isolated from periodontitis-affected periodontal ligament tissue (P-PDLSCs) was significantly lower than that of MSCs isolated from healthy human periodontal ligament tissue (H-PDLSCs). Inflammation in the microenvironment resulted in an inhibition of miR-17 levels, and a perturbation in the expression of miR-17 partly reversed the differentiation potential of PDLSCs in this microenvironment. Furthermore, inflammation in the microenvironment promoted the expression of Smad ubiquitin regulatory factor one (Smurf1), an important negative regulator of MSC osteogenic differentiation. Western blotting and 3' untranslated regions (3'-UTR) reporter assays confirmed that Smurf1 is a direct target of miR-17 in PDLSCs. Our data demonstrate that excessive inflammatory cytokine levels, miR-17, and Smurf1 were all involved in a coherent feed-forward loop. In this circuit,...