METTL14-mediated methylation of SLC25A3 mitigates mitochondrial damage in osteoblasts, leading to the improvement of osteoporosis

IF 3.9

Experimental gerontology Pub Date : 2024-06-25 DOI:10.1016/j.exger.2024.112496

Ping Wang , Weifeng Zhou , Fuhua Chen , Xiaoping Zhang , Qiu Zhang , Yiqing Chen , Nan Zhang

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引用次数: 0

Abstract

Purpose

Osteoporosis is linked to impaired function of osteoblasts, and decreased expression of METTL14 may result in abnormal differentiation of these bone-forming cells. However, the specific impact of METTL14 on osteoblast differentiation and its underlying mechanisms are not yet fully understood.

Methods and results

This study discovered a positive correlation between METTL14 expression and bone formation in specimens from osteoporosis patients and ovariectomized (OVX) mice. Additionally, METTL14 targeting of SLC25A3 contributed to the restoration of mitochondrial ROS levels and mitochondrial membrane potential in osteoblasts and promoted osteoblast differentiation. Moreover, in vivo experiments showed that METTL14 enhanced bone formation, and therapeutic introduction of METTL14 countered the decrease in bone formation in OVX mice.

Conclusions

Overall, these findings emphasize the crucial role of the METTL14/SLC25A3 signaling axis in osteoblast activity, suggesting that this axis could be a potential target for improving osteoporosis.

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METTL14 介导的 SLC25A3 甲基化可减轻成骨细胞线粒体损伤，从而改善骨质疏松症。

目的：骨质疏松症与成骨细胞功能受损有关，METTL14的表达减少可能导致这些成骨细胞的异常分化。然而，METTL14对成骨细胞分化的具体影响及其内在机制尚不完全清楚：本研究发现，在骨质疏松症患者和卵巢切除（OVX）小鼠的标本中，METTL14 的表达与骨形成呈正相关。此外，METTL14靶向SLC25A3有助于恢复成骨细胞线粒体ROS水平和线粒体膜电位，并促进成骨细胞分化。此外，体内实验表明，METTL14能促进骨形成，而治疗性引入METTL14能抵消OVX小鼠骨形成的减少：总之，这些发现强调了METTL14/SLC25A3信号轴在成骨细胞活性中的关键作用，表明该信号轴可能是改善骨质疏松症的潜在靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental gerontology Ageing, Biochemistry, Geriatrics and Gerontology

CiteScore

6.70

自引率

0.00%

发文量

审稿时长

66 days