MiR-17-3p inhibits osteoblast differentiation by downregulating Sox6 expression
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Isolation of Mesenchymal Stem Cells from Human Alveolar Periosteum and Effects of Vitamin D on Osteogenic Activity of Periosteum-derived Cells
Published on: May 4, 2018
1Department of Orthopedics, the First Affiliated Hospital of Kunming Medical University, Kunming, China.
Abstract:
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.
Insights
MicroRNA miR-17-3p is downregulated during osteoblast differentiation, inhibiting bone formation by targeting Sox6. This discovery offers new therapeutic strategies for orthopedic disorders like osteoporosis.
Area of Science:
- Biochemistry
- Molecular Biology
- Orthopedics
Background:
- Osteoporosis and osteoarthritis are prevalent orthopedic disorders in the elderly.
- Stimulating bone formation is a key therapeutic approach for these conditions.
- Osteoblasts are crucial for bone reconstruction, making their differentiation a target for therapeutic intervention.
Purpose of the Study:
- To investigate the role of microRNA miR-17-3p in osteoblast differentiation.
- To elucidate the mechanism by which miR-17-3p regulates osteogenesis.
- To explore potential therapeutic implications for orthopedic disorders.
Main Methods:
- Established an in vitro osteogenesis model using MC3T3-E1 cells treated with bone morphogenetic protein 2 (BMP2).
- Quantified miR-17-3p expression using reverse transcription-quantitative PCR.
- Assessed osteoblast differentiation via Alizarin Red staining, alkaline phosphatase (ALP) activity assays, and gene expression analysis of osteogenic markers.
- Identified and validated miR-17-3p target genes using bioinformatics analysis and luciferase reporter assays.
- Performed rescue experiments to confirm the role of SRY-box transcription factor 6 (Sox6).
Main Results:
- miR-17-3p expression was downregulated during BMP2-induced osteoblast differentiation in MC3T3-E1 cells.
- Downregulation of miR-17-3p correlated with reduced osteoblast differentiation, mineralization, ALP activity, and expression of osteogenesis-related genes.
- Sox6 was identified as a direct target gene of miR-17-3p.
- miR-17-3p inhibited osteoblast differentiation through its regulation of Sox6.
Conclusions:
- A novel mechanism of miRNA-mediated regulation of osteogenesis involving miR-17-3p and Sox6 was identified.
- The findings suggest that miR-17-3p plays an inhibitory role in osteoblast differentiation.
- This research provides potential therapeutic targets for treating orthopedic disorders characterized by impaired bone formation.
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