Irisin reshapes bone metabolic homeostasis to delay age-related osteoporosis by regulating the multipotent differentiation of BMSCs via Wnt pathway.

IF 3.9 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Frontiers in Molecular Biosciences Pub Date : 2025-01-07 eCollection Date: 2024-01-01 DOI:10.3389/fmolb.2024.1524978

Shangman Xing, Yifan Ma, Bing Song, Min Bai, Kexin Wang, Wenjing Song, Tingting Cao, Chao Guo, Yanying Zhang, Zhandong Wang, Yongfeng Wang

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引用次数: 0

Abstract

Introduction: Bone aging is linked to changes in the lineage differentiation of bone marrow stem cells (BMSCs), which show a heightened tendency to differentiate into adipocytes instead of osteoblasts. The therapeutic potential of irisin in addressing age-related diseases has garnered significant attention. More significantly, irisin has the capacity to enhance bone mass recovery and sustain overall bone health. Its mechanism of action in preventing osteoporosis has generated considerable interest within the research community. Nonetheless, the targeting effect of irisin on age-related osteoporosis and its underlying molecular biological mechanisms remain unclear.

Methods: The specific role of irisin in osteogenic-adipogenic differentiation in young or aging BMSCs was evaluated by multiple cells staining and quantitative real-time PCR (RT-qPCR) analysis. RNA-seq and protein Western blotting excavated and validated the key pathway by which irisin influences the fate determination of aging BMSCs. The macroscopic and microscopic changes of bone tissue in aging mice were examined using Micro-computed tomography (Micro-CT) and morphological staining.

Results: It was noted that irisin affected the multilineage differentiation of BMSCs in a manner dependent on the dosage. Simultaneously, the Wnt signaling pathway might be a crucial mechanism through which irisin sustains the bone-fat balance in aging BMSCs and mitigates the decline in pluripotency. In vivo, irisin reduced bone marrow fat deposition in aging mice and effectively alleviating the occurrence of bone loss.

Conclusion: Irisin mediates the Wnt signaling pathway, thereby influencing the fate determination of BMSCs. In addition, it is essential for preserving metabolic equilibrium in the bone marrow microenvironment and significantly contributes to overall bone health. The findings provide new evidence for the use of iris extract in the treatment of age-related osteoporosis.

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鸢尾素通过Wnt通路调节骨髓间质干细胞多能分化，重塑骨代谢稳态，延缓年龄相关性骨质疏松。

骨老化与骨髓干细胞（BMSCs）谱系分化的变化有关，BMSCs更倾向于分化为脂肪细胞而不是成骨细胞。鸢尾素在处理与年龄有关的疾病方面的治疗潜力已经引起了极大的关注。更重要的是，鸢尾素具有增强骨量恢复和维持整体骨骼健康的能力。其预防骨质疏松的作用机制在研究界引起了相当大的兴趣。然而，鸢尾素对老年性骨质疏松的靶向作用及其潜在的分子生物学机制尚不清楚。方法：采用多细胞染色和实时荧光定量PCR （RT-qPCR）方法，评价鸢尾素在年轻或衰老骨髓间充质干细胞成骨-脂肪分化中的具体作用。RNA-seq和蛋白Western blotting挖掘并验证了鸢尾素影响衰老骨髓间充质干细胞命运决定的关键途径。采用显微计算机断层扫描（Micro-CT）和形态学染色技术观察衰老小鼠骨组织的宏观和微观变化。结果：鸢尾素对骨髓间充质干细胞的多系分化有不同剂量的影响。同时，Wnt信号通路可能是鸢尾素维持老化骨髓间充质干细胞中骨脂平衡和减轻多能性下降的关键机制。在体内，鸢尾素可减少衰老小鼠骨髓脂肪沉积，有效缓解骨质流失的发生。结论：鸢尾素介导Wnt信号通路，影响骨髓间充质干细胞命运的决定。此外，它对维持骨髓微环境中的代谢平衡至关重要，并对整体骨骼健康有重要贡献。研究结果为虹膜提取物治疗老年性骨质疏松症提供了新的依据。

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

Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

7.20

自引率

4.00%

发文量

1361

审稿时长

14 weeks

期刊介绍： Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.