Department of Orthodontics, School of Stomatology, Shandong University, Jinan, People's Republic of China.
Shandong Provincial Key Laboratory of oral tissue regeneration, School of Stomatology, Shandong University, Jinan, People's Republic of China.
Sci Rep. 2017 Nov 30;7(1):16608. doi: 10.1038/s41598-017-16720-8.
Human periodontal ligament stem cells (hPDLSCs) are mesenchymal stem cells (MSCs) derived from dental and craniofacial tissues that exhibit high potential for differentiation into osteoblasts. Recently, microRNAs (miRNAs) have been established to play important roles in MSC osteogenesis. In the current study, we report that miR-21 was down-regulated in osteogenically differentiated PDLSCs. Overexpression of miR-21 significantly inhibited osteogenesis of hPDLSC, whereas its inhibition demonstrated the opposite effects. Furthermore, SMAD family member 5 (Smad5) was predicted to be a downstream target of miR-21 and was shown to undergo up-regulation in PDLSCs induced toward osteogenesis. Moreover, Smad5 and Runx2, which are the critical transcription factors in osteogenic differentiation, were predicted to be targets of miR-21. Suppression of miR-21 expression increased the level of Smad5 in vitro and during in vivo transplantation experiments. Furthermore, suppression of Smad5 inhibited osteogenic differentiation and decreased the protein level of Runx2. Taken together, these results suggested that miR-21 be mechanistically implicated in the regulation of osteogenic differentiation of hPDLSCs by targeting Smad5.
人牙周韧带干细胞（hPDLSCs）是来源于牙齿和颅面组织的间充质干细胞（MSCs），具有向成骨细胞分化的高潜力。最近，microRNAs（miRNAs）已被证实在 MSC 成骨分化中发挥重要作用。在本研究中，我们报告 miR-21 在成骨分化的 PDLSCs 中下调。miR-21 的过表达显著抑制 hPDLSC 的成骨分化，而其抑制作用则表现出相反的效果。此外，SMAD 家族成员 5（Smad5）被预测为 miR-21 的下游靶标，并显示在诱导向成骨分化的 PDLSCs 中上调。此外，Smad5 和 Runx2 是成骨分化中的关键转录因子，被预测为 miR-21 的靶标。抑制 miR-21 的表达水平增加了体外和体内移植实验中 Smad5 的水平。此外，抑制 Smad5 抑制成骨分化并降低 Runx2 的蛋白水平。总之，这些结果表明 miR-21 通过靶向 Smad5 参与调控 hPDLSCs 的成骨分化。
