多组学分析显示,VDR 是间充质干细胞衰老的核心调节因子,已知与高脂饮食暴露后的骨质疏松症有关

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE International Journal of Oral Science Pub Date : 2024-05-22 DOI:10.1038/s41368-024-00309-9
Jiayao Chen, Shuhong Kuang, Jietao Cen, Yong Zhang, Zongshan Shen, Wei Qin, Qiting Huang, Zifeng Wang, Xianling Gao, Fang Huang, Zhengmei Lin
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引用次数: 0

摘要

高脂饮食(HFD)与骨质疏松症和脆性骨折风险增加有关。然而,高脂饮食诱发骨质疏松症的具体机制尚未完全明了。我们的研究表明,暴露于HFD会诱导骨髓间充质干细胞(BMSCs)过早衰老,降低其增殖和成骨能力,从而导致骨质疏松症。转录组和染色质可及性分析表明,维生素 D 受体(VDR)结合序列的染色质可及性降低,高密度脂蛋白胆固醇喂养小鼠骨髓间充质干细胞中的 VDR 信号转导减少,这表明 VDR 是骨髓间充质干细胞衰老的关键调节因子。值得注意的是,给高密度脂蛋白胆固醇喂养的小鼠注射 VDR 激活剂能挽救 BMSC 的衰老,并显著改善成骨、骨量和其他骨参数。从机理上讲,VDR 激活通过降低细胞内活性氧(ROS)水平和保护线粒体功能来减少 BMSC 的衰老。我们的研究结果不仅阐明了高氟酸膳食诱导 BMSC 衰老和相关骨质疏松症的机制,还为通过靶向 VDR-superoxide dismutase 2 (SOD2)-ROS 轴治疗高氟酸膳食诱导的骨质疏松症提供了新的见解。
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Multiomics profiling reveals VDR as a central regulator of mesenchymal stem cell senescence with a known association with osteoporosis after high-fat diet exposure

The consumption of a high-fat diet (HFD) has been linked to osteoporosis and an increased risk of fragility fractures. However, the specific mechanisms of HFD-induced osteoporosis are not fully understood. Our study shows that exposure to an HFD induces premature senescence in bone marrow mesenchymal stem cells (BMSCs), diminishing their proliferation and osteogenic capability, and thereby contributes to osteoporosis. Transcriptomic and chromatin accessibility analyses revealed the decreased chromatin accessibility of vitamin D receptor (VDR)-binding sequences and decreased VDR signaling in BMSCs from HFD-fed mice, suggesting that VDR is a key regulator of BMSC senescence. Notably, the administration of a VDR activator to HFD-fed mice rescued BMSC senescence and significantly improved osteogenesis, bone mass, and other bone parameters. Mechanistically, VDR activation reduced BMSC senescence by decreasing intracellular reactive oxygen species (ROS) levels and preserving mitochondrial function. Our findings not only elucidate the mechanisms by which an HFD induces BMSC senescence and associated osteoporosis but also offer new insights into treating HFD-induced osteoporosis by targeting the VDR-superoxide dismutase 2 (SOD2)-ROS axis.

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来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
期刊介绍: The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.
期刊最新文献
Organoids in the oral and maxillofacial region: present and future. Personalized bioceramic grafts for craniomaxillofacial bone regeneration An unexpected role of neurite outgrowth inhibitor A as regulator of tooth enamel formation Periodontitis impacts on thrombotic diseases: from clinical aspect to future therapeutic approaches. CREB3L1 deficiency impairs odontoblastic differentiation and molar dentin deposition partially through the TMEM30B.
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