Downregulation of METTL14 improves postmenopausal osteoporosis via IGF2BP1 dependent posttranscriptional silencing of SMAD1

Huang, Chaoqing; Wang, Yuan

doi:10.1038/s41419-022-05362-y

Cited by 26 publications

(12 citation statements)

References 34 publications

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“…Postmenopausal ALP is a measure of bone formation and transformation, since release into the blood disrupts estrogen production, whereas elevated serum ALP activity reflects the activity of bone cell metabolic processes. 45 Ca and phosphorus in the blood reflect the physical structure of the bones. 46 Ca is an important mineral in the human body, of which 99% is found in the bones and teeth, and the remaining 1% is distributed in the blood, nerves, and various soft tissues.…”

Section: Discussionmentioning

confidence: 99%

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Eupatilin ameliorates postmenopausal osteoporosis via elevating microRNA‐211‐5p and repressing JAK2/STAT3 pathway

Hong,

Yang

2023

Environmental Toxicology

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Postmenopausal osteoporosis (PMOP) poses a significant threat to women's health worldwide. Eupatilin is a key bioactive component of the Chinese herbal medicine Artemisia asiatica Nakai. Recent research reports have proved the inhibitory function of Eupatilin in many diseases. MicroRNAs (miRNAs) are 21–23 nucleotide‐long, single‐stranded, noncoding RNA molecules generated endogenously, and many studies have indicated that miRNAs are involved in the development of osteoporosis. This study explored the role and potential mechanism of Eupatilin underlying PMOP. First, rats were given intragastric administration of Eupatilin every day and subcutaneous injections of oligonucleotides or plasmids that interfered with miR‐211‐5p or janus kinase 2 (JAK2) once a week. After 4 weeks, the PMOP rat model was established. Then, serum alkaline phosphatase, calcium, and phosphorus levels, as well as femur bone mineral density and biomechanical parameters, were detected. Hematoxylin–eosin staining and Masson staining were applied for detecting the pathological condition of femur, and immunohistochemical staining was for detecting osteocalcin. MC3T3‐E1 cells were transfected with plasmid vectors interfering with miR‐211‐5p or JAK2; and cell viability, lactate dehydrogenase cytotoxicity, and cell mineralization were subsequently examined. The relationship between miR‐211‐5p and JAK2/signal transducer and activator of transcription 3 (STAT3) pathway was analyzed. The targeting relation between miR‐211‐5p and JAK2 was also verified. The experimental results revealed that Eupatilin improved the pathological conditions of PMOP rats by promoting the proliferation and mineralization of osteoblasts. MiR‐211‐5p was down‐regulated and JAK2/STAT3 was upregulated in PMOP rats. Upregulation of miR‐211‐5p further improved the pathological conditions of PMOP rats based on Eupatilin treatment. MiR‐211‐5p inhibited the JAK2/STAT3 pathway. JAK2 offset the effects of elevated miR‐211‐5p on PMOP rats. Overall, Eupatilin attenuates PMOP through elevating miR‐211‐5p and repressing JAK2/STAT3 pathway, which suggests the utility of Eupatilin as a potential drug for POMP treatment.

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Section: Discussionmentioning

confidence: 99%

“…ALP is a measure of bone formation and transformation, since release into the blood disrupts estrogen production, whereas elevated serum ALP activity reflects the activity of bone cell metabolic processes 45 . Ca and phosphorus in the blood reflect the physical structure of the bones 46 .…”

Section: Discussionmentioning

confidence: 99%

Eupatilin ameliorates postmenopausal osteoporosis via elevating microRNA‐211‐5p and repressing JAK2/STAT3 pathway

Hong,

Yang

2023

Environmental Toxicology

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“…It has been proven that orbital adipose tissue is a main target of the autoimmune response (36). Most RNAs exhibit m6A methylation, which regulates a range of cellular biological functions such as immunological modulation, metabolism, stem cell maintenance, and body development (37). In a previous study, we demonstrated that m6A modi cation participated in the pathogenesis of TAO using surgically excised extraocular muscles (EOMs).…”

Section: Discussionmentioning

confidence: 99%

Analysis of N6-methyladenosine modification and immune infiltration characterization in thyroid associated ophthalmopathy

Yang

Zhu

et al. 2023

Preprint

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Background Thyroid-associated ophthalmopathy (TAO) is a potentially sight-threatening ocular disease that affects 50% of patients with Graves’ disease. N6-methyladenosine (m6A) modification is post-transcriptional RNA modification in mammalian mRNA. Exploring the role of m6A regulators and the immune infiltration characterization in TAO is essential to understand its pathogenesis. Methods We excavated differentially expressed m6A regulators from the TAO microarray data set (GSE58331) in the Gene Expression Omnibus (GEO). Based on R software (v4.2.2), we performed bioinformatics analyses including differential expression analysis, training models construction such as support vector machine (SVM), random forest (RF), and nomogram models for the evaluation of TAO occurrence, consensus clustering algorithm for the evaluation of clusters quantity, principal component analysis (PCA) for quantification of m6A modification level in individual patients, Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and single sample gene set enrichment analysis (ssGSEA) for functional enrichment analysis, etc. Results Four significant m6A regulators (IGFBP2, IGFBP3, RBM15B, and FTO) were screened by differential expression analysis between the TAO group and the healthy group. RM identified that the four m6A regulators above were associated with the risk of TAO. Furthermore, a nomogram was conducted to provide benefits to patients. Based on filtered m6A regulators, we divided the TAO group into two m6A subtypes (cluster A/B) by consensus clustering. The PCA algorithm calculated the m6A score of each sample to quantify m6A patterns. GO functional annotation proved that m6A-related differentially expressed genes (DEGs) enriched in biological processes (BP), cellular components (CC), and molecular functions (MF). KEGG enrichment analysis showed m6A-related DEGs were particularly abundant in the endocytosis, protein processing in endoplasmic reticulum, ubiquitin mediated proteolysis, and protein export. ssGSEA presented the difference in immune infiltration between m6Acluster A/B and gene cluster A/B. In addition, we also analyzed the relationship between m6Aclusters or gene clusters and cytokines. Conclusions This article analyzed the effect of m6A modification in the pathogenesis of TAO, focusing on immune infiltration. These findings may be able to guide the future strategy of immunotherapy.

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“…Although METTL14 only engages in the complex stabilization and RNA recruitment of MTC, it could promote osteogenesis of BMSCs in physiological and pathological conditions by stimulating m 6 A modification of multiple mRNAs including PTPN6 [ 51 ], TCF1 [ 52 ], Beclin-1 [ 53 ], and SMAD1 [ 54 ].…”

Section: A Modification and Osteogenesis Of Bmscsmentioning

confidence: 99%

N6-Methyladenosine in Cell-Fate Determination of BMSCs: From Mechanism to Applications

Zhang,

Li,

Wang

et al. 2024

Research

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The methylation of adenosine base at the nitrogen-6 position is referred to as “N6-methyladenosine (m 6 A)” and is one of the most prevalent epigenetic modifications in eukaryotic mRNA and noncoding RNA (ncRNA). Various m 6 A complex components known as “writers,” “erasers,” and “readers” are involved in the function of m 6 A. Numerous studies have demonstrated that m 6 A plays a crucial role in facilitating communication between different cell types, hence influencing the progression of diverse physiological and pathological phenomena. In recent years, a multitude of functions and molecular pathways linked to m 6 A have been identified in the osteogenic, adipogenic, and chondrogenic differentiation of bone mesenchymal stem cells (BMSCs). Nevertheless, a comprehensive summary of these findings has yet to be provided. In this review, we primarily examined the m 6 A alteration of transcripts associated with transcription factors (TFs), as well as other crucial genes and pathways that are involved in the differentiation of BMSCs. Meanwhile, the mutual interactive network between m 6 A modification, miRNAs, and lncRNAs was intensively elucidated. In the last section, given the beneficial effect of m 6 A modification in osteogenesis and chondrogenesis of BMSCs, we expounded upon the potential utility of m 6 A-related therapeutic interventions in the identification and management of human musculoskeletal disorders manifesting bone and cartilage destruction, such as osteoporosis, osteomyelitis, osteoarthritis, and bone defect.

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Downregulation of METTL14 improves postmenopausal osteoporosis via IGF2BP1 dependent posttranscriptional silencing of SMAD1

Cited by 26 publications

References 34 publications

Eupatilin ameliorates postmenopausal osteoporosis via elevating microRNA‐211‐5p and repressing JAK2/STAT3 pathway

Eupatilin ameliorates postmenopausal osteoporosis via elevating microRNA‐211‐5p and repressing JAK2/STAT3 pathway

Analysis of N6-methyladenosine modification and immune infiltration characterization in thyroid associated ophthalmopathy

N6-Methyladenosine in Cell-Fate Determination of BMSCs: From Mechanism to Applications

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