Osteosarcopenia: key molecular mechanisms and translational perspectives

Area of Science:

• Gerontology and Musculoskeletal Health
• Molecular Biology and Disease Mechanisms
• Regenerative Medicine and Nanotechnology

Background:

• Osteosarcopenia, characterized by the concurrent decline of bone and muscle mass, is a significant aging-related health concern.
• Research is evolving from single-organ pathology to understanding the complex interplay between bone and muscle in aging.
• A comprehensive understanding of osteosarcopenia's pathogenesis is crucial for developing effective interventions.

Purpose of the Study:

• To systematically elaborate on the pathogenesis of osteosarcopenia using an "intracellular - intercellular - systemic" hierarchical framework.
• To review and discuss emerging frontier interventions for osteosarcopenia with potential for clinical translation.
• To provide insights for precision prevention and treatment strategies for osteosarcopenia.

Main Methods:

• Literature review focusing on molecular mechanisms and interactions in osteosarcopenia.
• Systematic elaboration of pathogenesis through a hierarchical framework (intracellular, intercellular, systemic).
• Exploration of novel therapeutic targets and approaches, including nanoparticles, microRNAs, natural compounds, and biologics.

Main Results:

• A hierarchical framework elucidates the multidimensional molecular interactions underlying osteosarcopenia.
• Identified several promising frontier interventions: F6-(DSS)6-exo nanoparticles, miR-495, resveratrol, nuciferine, Clostridium butyricum, and bimagrumab.
• Highlighted the potential of these interventions for clinical application in managing osteosarcopenia.

Conclusions:

• Understanding the integrated pathogenesis of osteosarcopenia is key to developing targeted therapies.
• Future research should focus on the musculoskeletal microenvironment, advanced imaging for early detection, and biomaterials for regeneration.
• This review offers a foundation for advancing osteosarcopenia research and clinical practice.