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ORIGINAL RESEARCH article

Front. Mol. Biosci.
Sec. Cellular Biochemistry
Volume 11 - 2024 | doi: 10.3389/fmolb.2024.1524978
This article is part of the Research Topic Mechanism study of natural bioactive molecules using omics technology View all articles

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

Provisionally accepted
Shangman Xing Shangman Xing 1Yifan Ma Yifan Ma 2*Bing Song Bing Song 1,3*Min Bai Min Bai 4*Kexin Wang Kexin Wang 1Wenjing Song Wenjing Song 1*Tingting Cao Tingting Cao 1*Guo Chao Guo Chao 3*Yanying Zhang Yanying Zhang 3*Zhandong Wang Zhandong Wang 5*Yongfeng Wang Yongfeng Wang 1,6*
  • 1 The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, Gansu Province, China
  • 2 State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi’an, China
  • 3 Medicine Research and Experimental center, Gansu University of Chinese Medicine, Lanzhou, China
  • 4 Ningxia Medical University, Yinchuan, Ningxia, China
  • 5 Clinical College of Integrated Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, China
  • 6 Gansu Medical College, Pingliang, Gansu, China

The final, formatted version of the article will be published soon.

    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. RNAseq 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. Conclusions: 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.

    Keywords: Aging, BMSCs, irisin, Age-related osteoporosis, Bone-fat balance

    Received: 08 Nov 2024; Accepted: 16 Dec 2024.

    Copyright: © 2024 Xing, Ma, Song, Bai, Wang, Song, Cao, Chao, Zhang, Wang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Yifan Ma, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi’an, China
    Bing Song, The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, Gansu Province, China
    Min Bai, Ningxia Medical University, Yinchuan, 750004, Ningxia, China
    Wenjing Song, The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, Gansu Province, China
    Tingting Cao, The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, Gansu Province, China
    Guo Chao, Medicine Research and Experimental center, Gansu University of Chinese Medicine, Lanzhou, China
    Yanying Zhang, Medicine Research and Experimental center, Gansu University of Chinese Medicine, Lanzhou, China
    Zhandong Wang, Clinical College of Integrated Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, China
    Yongfeng Wang, The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, Gansu Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.