REVIEW article
Front. Endocrinol.
Sec. Bone Research
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1625806
This article is part of the Research TopicStem Cells and Extracellular Vesicles in Bone Health, Disease and Regeneration - Volume IIView all 3 articles
Mechanisms and Therapeutic Strategies Linking Mesenchymal Stem Cells Senescence to Osteoporosis
Provisionally accepted
- 1The First Clinical Medical College of Kunming Medical University, Kunming, Yunnan, China, Kunming, China
- 2The School of Basic Medical Sciences of Kunming Medical University, Kunming, Yunnan, China, Kunming, China
- 3The First Affiliated Hospital of Kunming Medical University, Kunming, China
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Osteoporosis is a common age-related bone metabolic disorder that significantly affects skeletal health, especially in aging populations. With global demographic shifts, the rising prevalence and disability burden of osteoporosis has placed increasing pressure on healthcare systems, making it a key area of research. A crucial factor in osteoporotic progression is the aging of mesenchymal stem cells (MSCs), which weakens bone regeneration through multiple mechanisms, including reduced osteogenic differentiation, heightened oxidative stress, chronic inflammation, and disrupted bone homeostasis. This review explores the intricate relationship between MSCs aging and osteoporosis development, focusing on key processes such as cell cycle arrest, telomere shortening, epigenetic changes, and osteogenic marker expression dysregulation. We also examine potential therapeutic strategies aimed at alleviating MSCs aging, including stem cell-based treatments, senolytic agents, inhibitors targeting the senescence-associated secretory phenotype, and biomaterial-assisted approaches such as extracellular vesicles and stimuli-responsive hydrogels. This review aims to provide insights into developing precise therapeutic strategies to restore MSCs function and slow bone loss. Furthermore, we discuss interdisciplinary approaches that link molecular mechanisms to practical applications, offering a broader perspective on addressing osteoporosis in aging societies.
Keywords: Mesenchymal Stem Cells, Aging, Osteoporosis Cellular Senescence, Bone Regeneration, senescence-associated secretory phenotype, Oxidative Stress
Received: 09 May 2025; Accepted: 30 Jun 2025.
Copyright: © 2025 Tong, Tu, Wang, Liu, Su, 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:
Yanghao Wang, The First Affiliated Hospital of Kunming Medical University, Kunming, China
Wei-zhou Wang, The First Affiliated Hospital of Kunming Medical University, Kunming, 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.