Myokines as Physiotherapy Rehabilitation Biomarkers: Molecular Mechanisms and Clinical Relevance in Musculoskeletal Disorders

Abstract

Background: Bioactive peptides and cytokines that are secreted from the skeletal muscle
during contraction have become important mediators of systemic adaptation during physiotherapy
guided rehabilitation. They have the ability to send signals across several organ systems and regulate
inflammation, anabolism, neuroplasticity and tissue repair, making them suitable biomarkers to track
musculoskeletal recovery.
Objective: The aim of this review is to collate existing evidence of the molecular mechanisms
involved in the secretion and action of myokines, focusing on the potential of myokines as biomarkers
in rehabilitation in 5 musculoskeletal diseases: osteoarthritis (OA), sarcopenia, tendinopathy, low back
pain (LBP), and post-surgical musculoskeletal rehabilitation.
Methods: An exhaustive search of literature was performed over PubMed, Scopus and Web
of Science from 2022 to 2025. Randomized controlled trials, systematic literature reviews, prospective
cohort studies and mechanistic in vitro or animal studies were included in the studies. 45 peer-
reviewed sources were used.
Results: The key myokines, interleukin-6 (IL-6), irisin, insulin-like growth factor-1 (IGF-1),
brain-derived neurotrophic factor (BDNF), myostatin, decorin and leukemia inhibitory factor (LIF)
show disorder-specific secretion patterns, receptor mediated signaling cascades, and gene expression
dynamics. The five disorders examined were found to have significant correlations between the levels
of the myokines and the functional rehabilitation results in clinical trials, quantitative data
In conclusion, myokine profiling is a non-invasive, repeatable approach to objectively monitor
the rehabilitation process within the physiotherapy approach. Standardization of measurement
protocols, setting up of reference ranges and prospective validation in multicenter trials are the most
salient steps towards clinical implementation.