当前位置：
X-MOL 学术
›
FEBS Open Bio
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
MiR-17-3p inhibits osteoblast differentiation by downregulating Sox6 expression.
FEBS Open Bio ( IF 2.8 ) Pub Date : 2020-09-18 , DOI: 10.1002/2211-5463.12979 Nan Chen 1 , Di Wu 1 , Hua Li 1 , Yi Liu 1 , Hao Yang 1
FEBS Open Bio ( IF 2.8 ) Pub Date : 2020-09-18 , DOI: 10.1002/2211-5463.12979 Nan Chen 1 , Di Wu 1 , Hua Li 1 , Yi Liu 1 , Hao Yang 1
Affiliation
|
Osteoporosis and osteoarthritis are orthopedic disorders that affect millions of elderly people worldwide; stimulation of bone formation is a potential therapeutic strategy for the treatment of these conditions. As the only bone‐forming cells, osteoblasts play a key role in bone reconstruction. The microRNA miR‐17‐3p is downregulated during osteogenic differentiation of human bone marrow mesenchymal stem cells, but its precise role in this process is unknown. Here, we investigated the role of miR‐17‐3p in osteoblast differentiation. An in vitro model of osteogenesis was established by treating MC3T3‐E1 murine preosteoblast cells with bone morphogenetic protein 2 (BMP2). The expression of miR‐17‐3p in BMP2‐induced MC3T3‐E1 cells was detected by reverse transcription‐quantitative PCR, and its effects on cells transfected with miR‐17‐3p mimic or inhibitor were evaluated by Alizarin Red staining, alkaline phosphatase (ALP) activity assay, and by detection of osteoblast markers including the ALP, collagen type I α1 chain, and osteopontin genes. Bioinformatics analysis was carried out to identify putative target genes of miR‐17‐3p, and the luciferase reporter assay was used for functional validation. Rescue experiments were performed to determine whether SRY‐box transcription factor 6 (Sox6) plays a role in the regulation of osteoblast differentiation by miR‐17‐3p. We report that miR‐17‐3p was downregulated upon BMP2‐induced osteoblast differentiation in MC3T3‐E1 cells, and this was accompanied by decreased differentiation and mineralization, ALP activity, and expression of osteogenesis‐related genes. Sox6 was confirmed to be a target gene of miR‐17‐3p in osteoblasts, and the inhibitory effect of miR‐17‐3p on osteoblast differentiation was observed to occur via Sox6. These results suggest the existence of a novel mechanism underlying miRNA‐mediated regulation of osteogenesis, which has potential implications for the treatment of orthopedic disorders.
中文翻译：
MiR-17-3p 通过下调 Sox6 表达来抑制成骨细胞分化。
骨质疏松症和骨关节炎是影响全世界数百万老年人的骨科疾病；刺激骨形成是治疗这些病症的潜在治疗策略。作为唯一的骨形成细胞，成骨细胞在骨重建中起着关键作用。microRNA miR-17-3p 在人骨髓间充质干细胞的成骨分化过程中下调，但其在此过程中的确切作用尚不清楚。在这里，我们研究了 miR-17-3p 在成骨细胞分化中的作用。体外_通过用骨形态发生蛋白 2 (BMP2) 处理 MC3T3-E1 小鼠前成骨细胞建立成骨模型。通过逆转录定量PCR检测miR-17-3p在BMP2诱导的MC3T3-E1细胞中的表达，并通过茜素红染色、碱性磷酸酶评估其对转染miR-17-3p模拟物或抑制剂的细胞的影响。 ALP) 活性测定，并通过检测包括 ALP、I 型胶原蛋白 α1 链和骨桥蛋白基因在内的成骨细胞标志物。进行生物信息学分析以鉴定 miR-17-3p 的推定靶基因，并使用荧光素酶报告基因测定进行功能验证。进行救援实验以确定 SRY-box 转录因子 6（Sox6) 在 miR-17-3p 调节成骨细胞分化中起作用。我们报告了 miR-17-3p 在 BMP2 诱导的 MC3T3-E1 细胞中的成骨细胞分化时被下调，这伴随着分化和矿化、ALP 活性和成骨相关基因表达的降低。Sox6被证实是 miR-17-3p 在成骨细胞中的靶基因，并观察到 miR-17-3p 对成骨细胞分化的抑制作用是通过Sox6发生的。这些结果表明，miRNA介导的成骨调节存在一种新机制，这对骨科疾病的治疗具有潜在意义。
更新日期：2020-11-04
中文翻译：
MiR-17-3p 通过下调 Sox6 表达来抑制成骨细胞分化。
骨质疏松症和骨关节炎是影响全世界数百万老年人的骨科疾病；刺激骨形成是治疗这些病症的潜在治疗策略。作为唯一的骨形成细胞，成骨细胞在骨重建中起着关键作用。microRNA miR-17-3p 在人骨髓间充质干细胞的成骨分化过程中下调，但其在此过程中的确切作用尚不清楚。在这里，我们研究了 miR-17-3p 在成骨细胞分化中的作用。体外_通过用骨形态发生蛋白 2 (BMP2) 处理 MC3T3-E1 小鼠前成骨细胞建立成骨模型。通过逆转录定量PCR检测miR-17-3p在BMP2诱导的MC3T3-E1细胞中的表达，并通过茜素红染色、碱性磷酸酶评估其对转染miR-17-3p模拟物或抑制剂的细胞的影响。 ALP) 活性测定，并通过检测包括 ALP、I 型胶原蛋白 α1 链和骨桥蛋白基因在内的成骨细胞标志物。进行生物信息学分析以鉴定 miR-17-3p 的推定靶基因，并使用荧光素酶报告基因测定进行功能验证。进行救援实验以确定 SRY-box 转录因子 6（Sox6) 在 miR-17-3p 调节成骨细胞分化中起作用。我们报告了 miR-17-3p 在 BMP2 诱导的 MC3T3-E1 细胞中的成骨细胞分化时被下调，这伴随着分化和矿化、ALP 活性和成骨相关基因表达的降低。Sox6被证实是 miR-17-3p 在成骨细胞中的靶基因，并观察到 miR-17-3p 对成骨细胞分化的抑制作用是通过Sox6发生的。这些结果表明，miRNA介导的成骨调节存在一种新机制，这对骨科疾病的治疗具有潜在意义。
京公网安备 11010802027423号