ArticleCell death and differentiation2015
miR-216a rescues dexamethasone suppression of osteogenesis, promotes osteoblast differentiation and enhances bone formation, by regulating c-Cbl-mediated PI3K/AKT pathway.
Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 135 citations in OpenAlex.
- SHED-Exo delivery of miR-708-5p activates PI3K/AKT signaling pathway to alleviate glucocorticoid-induced osteogenic inhibition in BMSCs.Molecular and cellular biochemistry · 2026Article
- Salvianolic acid B mitigates senescence and promotes osteogenesis of senescent bone marrow mesenchymal stem cells via the PI3K/AKT pathway.Biochemistry and biophysics reports · 2026Article
- Hyperoside Modulates the Estrogen-PI3K/VEGF Axis to Ameliorate Oxidative Damage-Induced Inhibition of Bone Formation in MC3T3-E1 Cells.Immunity, inflammation and disease · 2026Article
- TIGAR promotes osteogenic differentiation and ameliorates glucocorticoid-induced osteoporosis via autophagy-Nrf2-ROS axis.Genes & diseases · 2026Article
- Research progress on the regulation of miRNAs in diabetic kidney disease and osteoporosis.International journal of clinical and experimental pathology · 2026Review
- The E3 ligase c-Cbl modulates microglial phenotypes and contributes to Parkinson's disease pathology.Cell death discovery · 2025Article
- The Role of microRNA in the Regulation of Differentiation and the Functionality of Osteoblasts, Osteoclasts, and Their Precursors in Osteoporosis.Non-coding RNA · 2025Review
- CRE-Ter enhances murine bone differentiation, improves muscle cell atrophy, and increases irisin expression.PloS one · 2025Article
- Non-coding RNAs in osteoarthritis and osteoporosis-related hip fractures: molecular biomarkers for precision diagnosis and prognosis.Frontiers in endocrinology · 2025Review
- Article
- An adaptive biodegradable zinc alloy with bidirectional regulation of bone homeostasis for treating fractures and aged bone defects.Bioactive materials · 2024Article
- Heterogeneous DNA hydrogel loaded with Apt02 modified tetrahedral framework nucleic acid accelerated critical-size bone defect repair.Bioactive materials · 2024Article
- Surgical suction filter-derived bone graft displays osteogenic miRNA and mRNA patterns.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2024Article
- E3 ubiquitin ligases: key regulators of osteogenesis and potential therapeutic targets for bone disorders.Frontiers in cell and developmental biology · 2024Review
- Unveiling the unexplored novel signatures for osteoporosis via a detailed bioinformatics and molecular experiments based approach.American journal of translational research · 2024Article
- Long Noncoding RNA EMX2-AS Facilitates Osteoblast Differentiation and Bone Formation by Inhibiting EMX2 Protein Translation and Activating Wnt/Stem cells international · 2024Article
- Histone methyltransferase SETDB1 promotes osteogenic differentiation in osteoporosis by activating OTX2-mediated BMP-Smad and Wnt/β-catenin pathways.Human cell · 2023Article
- miRNA-Guided Regulation of Mesenchymal Stem Cells Derived from the Umbilical Cord: Paving the Way for Stem-Cell Based Regeneration and Therapy.International journal of molecular sciences · 2023Review
- Up-regulated and hypomethylated genes are causative factors and diagnostic markers of osteoporosis.American journal of translational research · 2023Article
- Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoporosis is a disease marked by reduced bone mass, leading to an increased risk of fractures or broken bones. Bone formation is mediated by recruiting mesenchymal stem cells (MSCs). Elucidation of the molecular mechanisms that regulate MSC differentiation into osteoblasts is of great importance for the development of anabolic therapies for osteoporosis and other bone metabolism-related diseases. microRNAs (miRNAs) have been reported to have crucial roles in bone development, osteogenic differentiation and osteoporosis pathophysiology. However, to date, only a few miRNAs have been reported to enhance osteogenesis and regulate the suppressive effect of glucocorticoids on osteogenic differentiation. In this study, we discovered that miR-216a, a pancreatic-specific miRNA, was significantly upregulated during osteogenic differentiation in human adipose-derived MSCs (hAMSCs). The expression of miR-216a was positively correlated with the expression of bone formation marker genes in clinical osteoporosis samples. Functional analysis demonstrated that miR-216a can markedly promote osteogenic differentiation of hAMSCs, rescue the suppressive effect of dexamethasone (DEX) on osteogenic differentiation in vitro and enhance bone formation in vivo. c-Cbl, a gene that encodes a RING finger E3 ubiquitin ligase, was identified as a direct target of miR-216a. Downregulation of c-Cbl by short hairpin RNAs can mimic the promotion effects of miR-216a and significantly rescue the suppressive effects of DEX on osteogenesis. Pathway analysis indicated that miR-216a regulation of osteogenic differentiation occurs via the c-Cbl-mediated phosphatidylinositol 3 kinase (PI3K)/AKT pathway. The recovery effects of miR-216a on the inhibition of osteogenesis by DEX were attenuated after blocking the PI3K pathway. Thus, our findings suggest that miR-216a may serve as a novel therapeutic agent for the prevention and treatment of osteoporosis and other bone metabolism-related diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.