The Role of m6A in Osteoporosis and the Differentiation of Mesenchymal Stem Cells into Osteoblasts and Adipocytes

Zhang, Weifei; Tang, Ke; Lin, Jianjing; Liu, Peng; Guan, Zhiping; Deng, Jiapeng; Wang, Deli; Zeng, Hui

doi:10.2174/1574888x17666220621155341

Cited by 5 publications

(2 citation statements)

References 84 publications

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“…Osteoporosis is a common metabolic bone disease affected by genetic and environmental factors. It increases the risk of bone fragility and fracture, seriously affecting patients’ quality of life [ 23 , 24 ]. Maintaining the balance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation is important for the prevention of osteoporosis [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Carbamazepine regulates USP10 through miR-20a-5p to affect the deubiquitination of SKP2 and inhibit osteogenic differentiation

Wang,

Liu,

Niu

et al. 2023

J Orthop Surg Res

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Background Antiepileptic drugs (AEDs) harm bone health and are significantly associated with osteoporosis development. In this study, we aimed to explore the mechanisms involved in carbamazepine (CBZ) and microRNA (miR)-20a-5p/ubiquitin-specific peptidase 10 (USP10)/S-phase kinase-associated protein 2 (SKP2) axis in osteoporosis. Methods Human bone marrow mesenchymal stem cells (BMSCs) were treated with different concentrations of CBZ. Knocking down or overexpressing miR-20a-5p, USP10, and SKP2 cell lines were constructed. The expressions of miR-20a-5p, USP10, SKP2, runt-related transcription factor 2 (Runx2), Alkaline phosphatase (ALP), Osterix (Osx), osteocalcin (OCN) and Collagen I were detected with western blot (WB) and reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Alizarin Red S (ARS) staining was performed to measure calcium deposition. Dual-luciferase assay and RNA immunoprecipitation (RIP) were applied to verify the binding relationship between miR-20a-5p and USP10. USP10 and SKP2 combination was verified by Co-Immunopurification (Co-IP). The stability of the SKP2 protein was verified by Cycloheximide chase assay. Results CBZ could reduce cell activity. ALP activity and ARS staining were enhanced in the osteogenic induction (OM) group. The expressions of Runx2, ALP, Osx, OCN and Collagen I were increased. CBZ reduced miR-20a-5p expressions. Verification experiments showed miR-20a-5p could target USP10. USP10 increased SKP2 stability and promoted SKP2 expression. CBZ regulated miR-20a-5p/USP10/SPK2 and inhibited BMSCs osteogenic differentiation. Conclusions CBZ regulated USP10 through miR-20a-5p to affect the deubiquitination of SKP2 and inhibit osteogenic differentiation, which provided a new idea for osteoporosis treatment.

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Section: Discussionmentioning

confidence: 99%

Carbamazepine regulates USP10 through miR-20a-5p to affect the deubiquitination of SKP2 and inhibit osteogenic differentiation

Wang,

Liu,

Niu

et al. 2023

J Orthop Surg Res

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“…Methylation, including N1-methylation, 7-methylguanosine, 5methylcytosine and N6-methyladenosine, involving the addition of a methyl group to a molecule and plays a crucial role in a myriad of biological processes, particularly in regulating the multifaceted functions of RNA (92)(93)(94)(95)(96). Similar to the mechanisms governing 6mA methylation, the orchestration of m6A modifications on RNA involves a tripartite regulatory system.…”

Section: M6a Methylation In Autophagy Regulationmentioning

confidence: 99%

Epigenetic targeting of autophagy for cancer: DNA and RNA methylation

Lin,

Zhao,

Zheng

et al. 2023

Front. Oncol.

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Autophagy, a crucial cellular mechanism responsible for degradation and recycling of intracellular components, is modulated by an intricate network of molecular signals. Its paradoxical involvement in oncogenesis, acting as both a tumor suppressor and promoter, has been underscored in recent studies. Central to this regulatory network are the epigenetic modifications of DNA and RNA methylation, notably the presence of N6-methyldeoxyadenosine (6mA) in genomic DNA and N6-methyladenosine (m6A) in eukaryotic mRNA. The 6mA modification in genomic DNA adds an extra dimension of epigenetic regulation, potentially impacting the transcriptional dynamics of genes linked to autophagy and, especially, cancer. Conversely, m6A modification, governed by methyltransferases and demethylases, influences mRNA stability, processing, and translation, affecting genes central to autophagic pathways. As we delve deeper into the complexities of autophagy regulation, the importance of these methylation modifications grows more evident. The interplay of 6mA, m6A, and autophagy points to a layered regulatory mechanism, illuminating cellular reactions to a range of conditions. This review delves into the nexus between DNA 6mA and RNA m6A methylation and their influence on autophagy in cancer contexts. By closely examining these epigenetic markers, we underscore their promise as therapeutic avenues, suggesting novel approaches for cancer intervention through autophagy modulation.

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METTL14 upregulates TCF1 through m6A mRNA methylation to stimulate osteogenic activity in osteoporosis

Wang

Zou

et al. 2022

Human Cell

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The Role of m6A in Osteoporosis and the Differentiation of Mesenchymal Stem Cells into Osteoblasts and Adipocytes

Cited by 5 publications

References 84 publications

Carbamazepine regulates USP10 through miR-20a-5p to affect the deubiquitination of SKP2 and inhibit osteogenic differentiation

Carbamazepine regulates USP10 through miR-20a-5p to affect the deubiquitination of SKP2 and inhibit osteogenic differentiation

Epigenetic targeting of autophagy for cancer: DNA and RNA methylation

METTL14 upregulates TCF1 through m6A mRNA methylation to stimulate osteogenic activity in osteoporosis

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