Exosome‑mediated crosstalk between the cardiovascular and musculoskeletal systems: Mechanisms and therapeutic potential (Review)

Int J Mol Med. 2025 Sep;56(3):129. doi: 10.3892/ijmm.2025.5570. Epub 2025 Jun 27.

Abstract

The cardiovascular and musculoskeletal systems are two core systems essential for maintaining human physiological functions and their dynamic interactions play a critical role in overall health. Exosomes, nanosized vesicles released by cells, contain bioactive substances including microRNA, long non‑coding RNA, lipids and proteins and participate in the pathophysiological regulation of multiple organ systems by mediating intercellular communication. Bone‑derived exosomes ameliorate cardiovascular diseases through the regulation of oxidative stress, inflammatory responses and apoptosis. Conversely, cardiovascular‑derived exosomes enhance bone homeostasis by suppressing osteoclast activity or promoting osteogenic differentiation, but they may also exacerbate pathological progression in conditions such as osteoarthritis. Skeletal muscle‑derived exosomes protect cardiomyocytes in muscular dystrophy through functional molecules delivery. However, under pathological conditions such as sarcopenia, skeletal muscle‑derived exosomes may aggravate cardiac dysfunction by activating pro‑apoptotic signals. Similarly, cardiovascular‑derived exosomes exhibit dual roles in skeletal muscle regulation, promoting regeneration while potentially inducing atrophy during heart failure. In addition, exosomes demonstrate significant clinical value as diagnostic biomarkers and targeted drug delivery vehicles, both for early disease detection and regenerative therapies. The present review systematically outlined the mechanisms underlying exosome‑mediated bidirectional crosstalk between the cardiovascular and musculoskeletal systems and explores their clinical application potential. It provided theoretical insights and novel perspectives for further research into the pathogenesis and therapeutic strategies of cardiovascular and musculoskeletal diseases.

Keywords: cardiovascular system; clinical application; crosstalk; exosome; mechanism; musculoskeletal system.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases* / metabolism
  • Cardiovascular Diseases* / pathology
  • Cardiovascular Diseases* / therapy
  • Cardiovascular System* / metabolism
  • Cell Communication
  • Exosomes* / metabolism
  • Humans
  • Muscle, Skeletal / metabolism
  • Musculoskeletal Diseases* / metabolism
  • Musculoskeletal Diseases* / therapy
  • Musculoskeletal System* / metabolism