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Exercise‑induced exosomal noncoding RNAs: Molecular signaling cascades in bone remodeling and translational applications in sports‑related bone injuries (Review)

  • Authors:
    • Bin Tian
    • Xuesong Chen
    • Jiang Zheng
    • Xin Kang
  • View Affiliations / Copyright

    Affiliations: Sports Medicine Center, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, P.R. China
    Copyright: © Tian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 257
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    Published online on: July 14, 2026
       https://doi.org/10.3892/ijmm.2026.5928
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Abstract

Exercise has profound beneficial effects on bone health, yet the molecular mechanisms that mediate mechanical force transduction remain incompletely understood. Exosomal noncoding RNAs (ncRNAs) have emerged as critical intercellular messengers that translate mechanical stimuli into coordinated signaling cascades within the bone microenvironment. The present review systematically synthesizes evidence demonstrating that exercise dynamically modulates exosomal ncRNA expression in a modality‑dependent and temporally regulated manner. These exercise‑induced exosomal ncRNAs orchestrate bone remodeling by activating osteogenic pathways such as the Wnt/β‑catenin pathway, suppressing osteoclastogenesis via receptor activator of nuclear factor κB (RANK) ligand (RANKL)/RANK/osteoprotegerin axis modulation, and coordinating multicellular interactions. Translational applications for sports‑related bone injuries are critically evaluated, including noninvasive biomarkers, personalized exercise prescriptions, and engineered exosome‑based therapeutics, alongside current limitations. Collectively, these findings support exercise‑induced exosomal ncRNAs as a central paradigm linking physical activity to skeletal adaptation.
View Figures

Figure 1

Schematic overview of the core triad:
Exercise, exosomal ncRNAs, and bone remodeling. Core framework
linking exercise, exosomal ncRNAs, and bone remodeling. Exercise
stimulates the release of exosomes containing miRNAs, lncRNAs, and
circRNAs, which regulate osteoblast-mediated osteogenesis and
osteoclast-mediated resorption to maintain skeletal homeostasis.
ncRNAs, noncoding RNAs; miRNAs, microRNAs; lncRNAs, long noncoding
RNAs; circRNAs, circular RNAs.

Figure 2

Exercise modulation of exosomal
ncRNAs: Regulatory patterns and tissue sources. Exercise modality,
tissue origin, dose parameters, individual factors, and temporal
dynamics collectively shape exosomal ncRNA profiles. ncRNAs,
noncoding RNAs; miRNA, microRNA; lncRNA, long noncoding RNA;
circRNA, circular RNA.

Figure 3

Molecular signaling cascades of
exercise-induced exosomal ncRNAs in bone remodeling. Mechanical
strain during exercise stimulates release of exosomes from skeletal
muscle and osteocytes. These exosomes carry ncRNAs (miRNAs,
lncRNAs, circRNAs) that activate osteogenic pathways
(Wnt/β-catenin, BMP/Smad, MAPK/ERK) in osteoblasts, suppress
osteoclastogenesis via RANKL/RANK/OPG and NF-κB/NFATc1 signaling,
and coordinate multi-cellular effects (BMSC lineage commitment,
angiogenesis, immune modulation). ncRNAs, noncoding RNAs; miRNAs,
microRNAs; lncRNAs, long noncoding RNAs; circRNAs, circular RNAs;
BMP, bone morphogenetic protein; MAPK, mitogen-activated protein
kinase; ERK, extracellular signal-regulated kinase; RANK, receptor
activator of nuclear factor-κB; RANKL, receptor activator of
nuclear factor-κB ligand; OPG, osteoprotegerin; NF-κB, nuclear
factor-κB; NFATc1, nuclear factor of activated T-cells 1; BMSC,
bone marrow mesenchymal stem cell.
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Copy and paste a formatted citation
Spandidos Publications style
Tian B, Chen X, Zheng J and Kang X: Exercise‑induced exosomal noncoding RNAs: Molecular signaling cascades in bone remodeling and translational applications in sports‑related bone injuries (Review). Int J Mol Med 58: 257, 2026.
APA
Tian, B., Chen, X., Zheng, J., & Kang, X. (2026). Exercise‑induced exosomal noncoding RNAs: Molecular signaling cascades in bone remodeling and translational applications in sports‑related bone injuries (Review). International Journal of Molecular Medicine, 58, 257. https://doi.org/10.3892/ijmm.2026.5928
MLA
Tian, B., Chen, X., Zheng, J., Kang, X."Exercise‑induced exosomal noncoding RNAs: Molecular signaling cascades in bone remodeling and translational applications in sports‑related bone injuries (Review)". International Journal of Molecular Medicine 58.3 (2026): 257.
Chicago
Tian, B., Chen, X., Zheng, J., Kang, X."Exercise‑induced exosomal noncoding RNAs: Molecular signaling cascades in bone remodeling and translational applications in sports‑related bone injuries (Review)". International Journal of Molecular Medicine 58, no. 3 (2026): 257. https://doi.org/10.3892/ijmm.2026.5928
Copy and paste a formatted citation
x
Spandidos Publications style
Tian B, Chen X, Zheng J and Kang X: Exercise‑induced exosomal noncoding RNAs: Molecular signaling cascades in bone remodeling and translational applications in sports‑related bone injuries (Review). Int J Mol Med 58: 257, 2026.
APA
Tian, B., Chen, X., Zheng, J., & Kang, X. (2026). Exercise‑induced exosomal noncoding RNAs: Molecular signaling cascades in bone remodeling and translational applications in sports‑related bone injuries (Review). International Journal of Molecular Medicine, 58, 257. https://doi.org/10.3892/ijmm.2026.5928
MLA
Tian, B., Chen, X., Zheng, J., Kang, X."Exercise‑induced exosomal noncoding RNAs: Molecular signaling cascades in bone remodeling and translational applications in sports‑related bone injuries (Review)". International Journal of Molecular Medicine 58.3 (2026): 257.
Chicago
Tian, B., Chen, X., Zheng, J., Kang, X."Exercise‑induced exosomal noncoding RNAs: Molecular signaling cascades in bone remodeling and translational applications in sports‑related bone injuries (Review)". International Journal of Molecular Medicine 58, no. 3 (2026): 257. https://doi.org/10.3892/ijmm.2026.5928
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