Tu Shaoqin, Chen Yihua, Feng Yi, Kuang Zhili, Wang Yuxuan, Chen Lin, Mai Zhihui, Wei Jiaming, Zhang Sai, Shao Yiting, Ai Hong, Chen Zheng
Department of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Department of Stomatology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
Stem Cells Int. 2023 Mar 3;2023:5671809. doi: 10.1155/2023/5671809. eCollection 2023.
Periodontal ligament stem cells (PDLSCs) are considered ideal cell sources for the regeneration of periodontal and alveolar bone tissue. Cytoskeleton Regulator RNA (), a newly discovered long noncoding RNA, has been reported to function as competing endogenous RNA (ceRNA) and to be involved in many biological processes. However, its roles in PDLSC osteogenic differentiation remain unclear. Here, we firstly found was mainly sublocalized in the cytoplasm of PDLSCs and expression was increased during osteogenic differentiation of PDLSCs. By employing gain- and loss-of-function approaches, we then identified overexpression promoted osteogenic differentiation of PDLSCs while knockdown inhibited this process. Furthermore, bioinformatics analysis was utilized to show that both and mRNA contained the same seed sites for miR-6512-3p, which was further confirmed by dual luciferase reporter assay and RNA-binding protein immunoprecipitation. Notably, conferred its functions by directly binding to miR-6512-3p and an inverse correlation between and miR-6512-3p on the level on SOX11 and osteogenic differentiation of PDLSCs was obtained. Additionally, miR-6512-3p could bind to mRNA 3' UTR and repressed SOX11 expression. Moreover, level of SOX11 was significantly increased during osteogenic differentiation of PDLSCs. Knockdown of SOX11 attenuated the increasing effect of overexpression on osteogenic differentiation of PDLSCs. Collectively, these data supported that positively modulated the expression of SOX11 through competitively binding to miR-6512-3p, thus promoting osteogenic differentiation of PDLSCs. The /miR-6512-3p/SOX11 axis could be a novel therapeutic target for periodontal regeneration medicine.
牙周膜干细胞(PDLSCs)被认为是牙周和牙槽骨组织再生的理想细胞来源。细胞骨架调节RNA()是一种新发现的长链非编码RNA,据报道它作为竞争性内源RNA(ceRNA)发挥作用,并参与许多生物学过程。然而,其在PDLSC成骨分化中的作用仍不清楚。在此,我们首先发现主要定位于PDLSCs的细胞质中,并且在PDLSCs的成骨分化过程中其表达增加。通过采用功能获得和功能缺失方法,我们随后确定过表达促进了PDLSCs的成骨分化,而敲低则抑制了这一过程。此外,利用生物信息学分析表明和mRNA包含相同的miR-6512-3p种子位点,双荧光素酶报告基因测定和RNA结合蛋白免疫沉淀进一步证实了这一点。值得注意的是,通过直接结合miR-6512-3p发挥其功能,并且在SOX11水平和PDLSCs的成骨分化上与miR-6512-3p呈负相关。此外,miR-6512-3p可以与mRNA 3'UTR结合并抑制SOX11表达。而且,在PDLSCs的成骨分化过程中SOX11水平显著增加。敲低SOX11减弱了过表达对PDLSCs成骨分化的增强作用。总的来说,这些数据支持通过竞争性结合miR-6512-3p正向调节SOX11的表达,从而促进PDLSCs的成骨分化。/miR-6512-3p/SOX11轴可能是牙周再生医学的一个新的治疗靶点。