Department of Orthopaedics, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Eur Rev Med Pharmacol Sci. 2020 Jan;24(2):526-534. doi: 10.26355/eurrev_202001_20029.
To elucidate the role of telomerase RNA elements (TERC) in alleviating osteoporosis (OP) by absorbing microRNA-217 (miRNAs-217) to regulate runt-related transcription factor 2 (RUNX2) level.
The serum levels of TERC and miRNA-217 in OP patients and healthy controls were determined. During the osteogenic process, the relative levels of alkaline phosphatase (ALP), RUNX2, and Osterix were determined in hMSCs. The regulatory effects of TERC, miRNA-217, and RUNX2 on ALP and RUNX2 levels in hMSCs were examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. In addition, the changes in ALP activity and calcification ability in hMSCs influenced by them were assessed through ALP activity determination and alizarin red staining, respectively. The interaction of TERC/miRNA-217/RUNX2 regulatory loop and its role in influencing hMSCs osteogenesis were assessed by Dual-Luciferase Reporter Gene Assay and a series of rescue experiments, respectively.
The downregulated TERC and upregulated miRNA-217 were identified in the serum of the OP patients. Consistently, the downregulated TERC and upregulated miRNA-217 were discovered in in vitro osteogenic process of hMSCs. The silence of TERC, or RUNX2 downregulated ALP and RUNX2 levels, decreased ALP activity and attenuated the calcification ability in hMSCs. The overexpression of miRNA-217 gave similar results. The binding relationship in TERC/miRNA-217/RUNX2 regulatory loop was verified. At last, rescue experiments suggested that TERC accelerated hMSCs osteogenesis by absorbing miRNA-217 to upregulate RUNX2.
The serum level of TERC is lowly expressed in OP patients. TERC influences hMSCs osteogenesis by absorbing miRNA-217 to upregulate RUNX2, thus alleviating the progression of OP.
通过吸收 microRNA-217（miRNAs-217）来调节 runt 相关转录因子 2（RUNX2）水平，阐明端粒酶 RNA 元件（TERC）在缓解骨质疏松症（OP）中的作用。
检测 OP 患者和健康对照者血清中 TERC 和 miRNA-217 的水平。在成骨过程中，检测 hMSCs 中碱性磷酸酶（ALP）、RUNX2 和 Osterix 的相对水平。通过定量实时聚合酶链反应（qRT-PCR）和 Western blot 检测 TERC、miRNA-217 和 RUNX2 对 hMSCs 中 ALP 和 RUNX2 水平的调节作用。此外，通过 ALP 活性测定和茜素红染色分别评估它们对 hMSCs 中 ALP 活性和钙化能力的影响。通过双荧光素酶报告基因检测评估 TERC/miRNA-217/RUNX2 调控环路的变化及其对 hMSCs 成骨的影响，并通过一系列挽救实验进行评估。
OP 患者血清中 TERC 下调，miRNA-217 上调。在 hMSCs 的体外成骨过程中，也发现了 TERC 的下调和 miRNA-217 的上调。沉默 TERC 或下调 RUNX2 均可降低 ALP 和 RUNX2 水平，降低 ALP 活性，减弱 hMSCs 的钙化能力。过表达 miRNA-217 也得到了类似的结果。验证了 TERC/miRNA-217/RUNX2 调控环路中的结合关系。最后，挽救实验表明 TERC 通过吸收 miRNA-217 上调 RUNX2 加速 hMSCs 成骨。
OP 患者血清中 TERC 表达水平较低。TERC 通过吸收 miRNA-217 来上调 RUNX2 影响 hMSCs 成骨，从而缓解 OP 的进展。
