Mechanisms and therapeutic strategies linking mesenchymal stem cells senescence to osteoporosis

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...

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Main Authors: Yashuang Tong, Yulin Tu, Jingying Wang, Xiuyu Liu, Qian Su, Yanghao Wang, Weizhou Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1625806/full
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author Yashuang Tong
Yashuang Tong
Yulin Tu
Yulin Tu
Jingying Wang
Xiuyu Liu
Qian Su
Yanghao Wang
Yanghao Wang
Weizhou Wang
author_facet Yashuang Tong
Yashuang Tong
Yulin Tu
Yulin Tu
Jingying Wang
Xiuyu Liu
Qian Su
Yanghao Wang
Yanghao Wang
Weizhou Wang
author_sort Yashuang Tong
collection DOAJ
description 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.
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series Frontiers in Endocrinology
spelling doaj-art-cd8b6f6e24db4ea797ba7de22618058b2025-08-20T03:28:17ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-07-011610.3389/fendo.2025.16258061625806Mechanisms and therapeutic strategies linking mesenchymal stem cells senescence to osteoporosisYashuang Tong0Yashuang Tong1Yulin Tu2Yulin Tu3Jingying Wang4Xiuyu Liu5Qian Su6Yanghao Wang7Yanghao Wang8Weizhou Wang9Department of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaFirst School of Clinical Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaFirst School of Clinical Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaFirst School of Clinical Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaFirst School of Clinical Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaFirst School of Clinical Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Pathology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaOsteoporosis 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.https://www.frontiersin.org/articles/10.3389/fendo.2025.1625806/fullmesenchymal stem cellsagingosteoporosis cellular senescencebone regenerationsenescence-associated secretory phenotypeoxidative Stress
spellingShingle Yashuang Tong
Yashuang Tong
Yulin Tu
Yulin Tu
Jingying Wang
Xiuyu Liu
Qian Su
Yanghao Wang
Yanghao Wang
Weizhou Wang
Mechanisms and therapeutic strategies linking mesenchymal stem cells senescence to osteoporosis
Frontiers in Endocrinology
mesenchymal stem cells
aging
osteoporosis cellular senescence
bone regeneration
senescence-associated secretory phenotype
oxidative Stress
title Mechanisms and therapeutic strategies linking mesenchymal stem cells senescence to osteoporosis
title_full Mechanisms and therapeutic strategies linking mesenchymal stem cells senescence to osteoporosis
title_fullStr Mechanisms and therapeutic strategies linking mesenchymal stem cells senescence to osteoporosis
title_full_unstemmed Mechanisms and therapeutic strategies linking mesenchymal stem cells senescence to osteoporosis
title_short Mechanisms and therapeutic strategies linking mesenchymal stem cells senescence to osteoporosis
title_sort mechanisms and therapeutic strategies linking mesenchymal stem cells senescence to osteoporosis
topic mesenchymal stem cells
aging
osteoporosis cellular senescence
bone regeneration
senescence-associated secretory phenotype
oxidative Stress
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1625806/full
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