LncRNA TERC alleviates the progression of osteoporosis by absorbing miRNA-217 to upregulate RUNX2

摘要

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.