Epigenetic Mechanisms in Osteoporosis: Exploring the Power of m⁶A RNA Modification

Journal of Cellular and Molecular Medicine, Год журнала: 2025, Номер 29(1)

Опубликована: Янв. 1, 2025

ABSTRACT Osteoporosis, recognised as a metabolic disorder, has emerged significant burden on global health. Although available treatments have made considerable advancements, they remain inadequately addressed. In recent years, the role of epigenetic mechanisms in skeletal disorders garnered substantial attention, particularly concerning m 6 A RNA modification. is most prevalent dynamic and reversible modification eukaryotes, mediating various processes mRNAs, including splicing, structural conversion, translation, translocation degradation serves crucial component Research increasingly validated that plays vital proliferation, differentiation, migration, invasion,and repair bone marrow mesenchymal stem cells (BMSCs), osteoblasts osteoclasts, all which impact whole process osteoporosis pathogenesis. Continuous efforts been to target regulators natural products derived from traditional medicine, exhibit multiple biological activities such anti‐inflammatory anticancer effects, valuable resources for drug discovery. This paper elaborates methylation its regulatory osteoporosis, emphasising implications diagnosis treatment, thereby providing theoretical references.

Язык: Английский

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Causal Relationship Between Blood Metabolites and Osteoporosis: A Two-Sample Mendelian Randomization and Genetic Correlation Analysis

Bioengineering, Год журнала: 2025, Номер 12(5), С. 435 - 435

Опубликована: Апрель 22, 2025

Background: Osteoporosis (OP) is a systemic bone disease often undiagnosed until fractures occur. Metabolites may influence OP, offering potential biomarkers or therapeutic targets. This study investigates the causal relationship between circulating metabolites and OP-related phenotypes using Mendelian Randomization (MR). Methods: GWAS data on 233 metabolic traits from 136,016 participants were analyzed through two-sample MR. Linkage disequilibrium score regression (LDCS) was used to estimate genetic correlations phenotypes, leveraging European ancestry linkage scores account for polygenicity stratification. MR employed inverse-variance weighted (IVW) method, with sensitivity analyses via MR-Egger, MR-PRESSO, median methods address pleiotropy confounders. Results: LDCS identified significant mineral density (BMD) total body BMD (toBMD) showing strongest associations. Thirty-five metabolite traits, including apolipoprotein A-I, exhibited linkages. Among 79 influencing BMD, serum acetate levels significantly associated femoral neck (OR: 1.28, 95% CI: 1.02–1.62), lumbar spine 1.73, 1.32–2.27), 1.21, 1.04–1.42). Creatinine consistently linked reduced 0.88, 0.79–0.99). Triglycerides in IDL VLDL particles also contributed variation. Conclusions: Significant relationships observed specific highlighting key as of health. These findings enhance understanding OP pathogenesis suggest future preventive strategies.

Язык: Английский

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Mitochondria in skeletal system-related diseases

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 181, С. 117505 - 117505

Опубликована: Ноя. 4, 2024

Язык: Английский

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Metformin improves HPRT1-targeted purine metabolism and repairs NR4A1-mediated autophagic flux by modulating FoxO1 nucleocytoplasmic shuttling to treat postmenopausal osteoporosis

Cell Death and Disease, Год журнала: 2024, Номер 15(11)

Опубликована: Ноя. 6, 2024

Abstract Osteoporosis is a major degenerative metabolic bone disease that threatens the life and health of postmenopausal women. Owing to limitations in detection methods prevention strategy awareness, purpose osteoporosis treatment more delay further deterioration rather than fundamentally correct mass. We aimed clarify pathogenesis optimize plans. Our experiments were based on previous findings oxidative stress mediates metabolism imbalance after oestrogen deficiency. Through energy metabolism-targeted metabolomics, we revealed purine disorder main mechanism involved inducing damage tissue, which was verified via use machine-learning data from human databases. Xanthine xanthine oxidase used treat osteoblasts construct model. The activity differentiation ability decreased X/XO treatment. Transcriptomic sequencing indicated autophagic flux metabolism-induced osteoblasts. Additionally, performed serum metabolomics combined with network pharmacology determine pharmacological metformin osteoporosis. HPRT1 potential target filtered hub genes, FoxO1 signalling key pathway mediating effect also SIRT3-mediated deacetylation promoted nuclear localization increase expression HPRT1. upregulation anabolism prevented accumulation ROS caused by catabolism reverse propose disorder-induced important for therapeutic should be confirmed through subsequent drug optimization development studies improve

Язык: Английский

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Nrf2 mediates the antioxidant and anti-osteoporotic effects of sinigrin.

Heliyon, Год журнала: 2024, Номер unknown, С. e39528 - e39528

Опубликована: Окт. 1, 2024

Язык: Английский

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