Melatonin inhibits adipogenesis and enhances osteogenesis of BMSCs through increasing KLF5 expression

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2025-07-21 DOI:10.1016/j.cellsig.2025.112017

Shenghong Wang , Cong Tian , Jinmin Liu , Zhiwei Feng , Dacheng Zhao , Ao Yang , Dejian Xiang , Changshun Chen , Yayi Xia , Bin Geng

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引用次数: 0

Abstract

Bone marrow-derived mesenchymal stem cells (BMSCs) maintain bone homeostasis by balancing adipogenesis and osteogenesis, with disruption of this balance favoring adipogenesis contributing to osteoporosis. Melatonin, known for regulating bone metabolism, promotes osteogenesis and inhibits adipogenesis, but the mechanisms remain unclear. This study investigates whether melatonin regulates BMSC differentiation by modulating the methylation of the Krüppel-like factor 5 (KLF5) promoter, a transcription factor involved in both adipogenesis and osteogenesis. Using an ovariectomy (OVX)-induced osteoporosis mouse model, we found that melatonin treatment significantly reversed OVX-induced bone loss, increased bone mineral density, and reduced bone marrow adiposity, accompanied by increased KLF5 expression in bone tissue. In vitro, melatonin promoted osteogenic differentiation and suppressed adipogenic differentiation in BMSCs, with decreased methylation of the KLF5 promoter. Knockdown of KLF5 suppressed osteogenesis and enhanced adipogenesis, while KLF5 overexpression promoted osteogenesis and inhibited adipogenesis. Melatonin-induced demethylation of the KLF5 promoter was associated with increased KLF5 expression, which in turn promoted osteogenic differentiation and inhibited adipogenic differentiation. These findings reveal a novel epigenetic mechanism underlying melatonin's bone-protective effects and suggest KLF5 promoter methylation as a potential therapeutic target for osteoporosis and related bone disorders.

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褪黑素通过增加KLF5的表达抑制骨髓间充质干细胞的脂肪生成和促进成骨

骨髓间充质干细胞（BMSCs）通过平衡脂肪生成和骨生成来维持骨稳态，而这种有利于脂肪生成的平衡被破坏会导致骨质疏松症。褪黑素具有调节骨代谢、促进成骨和抑制脂肪生成的作用，但其机制尚不清楚。本研究探讨褪黑激素是否通过调节kr样因子5 （KLF5）启动子的甲基化来调节BMSC分化，KLF5是一种参与脂肪形成和成骨形成的转录因子。使用卵巢切除术（OVX）诱导的骨质疏松小鼠模型，我们发现褪黑激素治疗显著逆转OVX诱导的骨质流失，增加骨密度，减少骨髓脂肪，同时增加骨组织中KLF5的表达。在体外，褪黑激素促进骨髓间充质干细胞成骨分化，抑制成脂分化，降低KLF5启动子的甲基化。低表达KLF5抑制成骨，促进脂肪生成，而过表达KLF5促进成骨，抑制脂肪生成。褪黑激素诱导的KLF5启动子的去甲基化与KLF5表达的增加有关，KLF5表达的增加反过来促进成骨分化并抑制脂肪分化。这些发现揭示了褪黑激素骨骼保护作用的一种新的表观遗传机制，并提示KLF5启动子甲基化是骨质疏松症和相关骨骼疾病的潜在治疗靶点。

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

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.