Circ_ 0006873 Sponges miR-142-5p to Inhibit Osteoblastic Differentiation of hBMSCs via Regulating PTEN/Akt Signaling Pathway
ANNALS OF CLINICAL AND LABORATORY SCIENCE(2022)
摘要
Objective. Osteoporosis is likely becoming a new disease challenge with increasing aging popula-tion. Circ_0006873 dysregulation may serve as an event linked to osteoporosis. Thus, this study sought to evaluate the function and mechanism of circ_0006873 on osteoporosis. Methods. Clinical serum samples collected from 30 osteoporosis patients were utilized to obtain circ_0006873 and miR-142-5p expression data. The link between circ_0006873, miR-142-5p, and phosphatase and tensin homolog (PTEN) was demonstrated via online tools (starBase, circinteractome), RNA Immunoprecipitation (RIP) and dual-Luciferase reporter assays. After knockdown or overexpression, cell counting kit-8 (CCK-8) assay measured cell viability. Alizarin red S (ARS) staining as well Alkaline phosphatase (ALP) staining detected osteoblas-tic differentiation levels. Quantitative real-time PCR (qRT-PCR) and western blot analyzed expression of RNAs and proteins after transfection or during osteoblastic differentiation. Results. circ_0006873 was upregulated in osteoporosis patients and decreased during osteoblastic differentiation. Following experi-ments revealed that cell viability, proliferation-related factors, osteogenic marker genes (ALP, Runx2, Bglap) and osteoblastic differentiation degree were promoted after circ_0006873 knockdown but inhibited after overexpression. Circ_0006873 sponged miR-142-5p, which was downregulated in osteoporosis patients and became higher during osteoblastic differentiation. Rescue assay indicated miR-142-5p mimic could reverse the effects of circ_0006873 overexpression on cell viability and osteogenic markers, and also could activate Akt pathway. Furthermore, circ_0006873 can negatively target miR-142-5p via regulating PTEN to inhibit osteoblastic differentiation. Conclusion. Circ_0006873 sponges miR-142-5p thereby enhances PTEN expression to suppress osteoblastic differentiation via regulation of Akt signaling pathway, thus, may provide a treatment approach for osteoporosis.
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关键词
osteoporosis, circ_0006873, miR-142-5p, Akt signaling pathway, phosphatase and tensin ho-molog, osteoblastic differentiation
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