This study aimed to test the hypothesis that mitochondrial dysfunction via the Piezo1/PGC-1α/MFN-1 pathway inactivation occurs in immobilized skeletal muscle, clarifying that these alterations were related to the muscle contracture mechanisms causing limited ROM.
Eight-week-old male Wistar rats were divided randomly into control groups (n = 20) and immobilization groups (n = 20), in which both ankle joints were immobilized at maximum plantar flexion using plaster casts for 1 or 2 weeks. The rats were anesthetized with an anesthetic agent, and the ROM of both ankle joint dorsiflexion was determined with a goniometer at each endpoint. Both soleus muscles were harvested after each experimental period. The right soleus muscles were used for nicotinamide adenine dinucleotide-tetrazolium reductase (NADH-TR) and succinate dehydrogenase (SDH) staining to assess mitochondrial homeostasis by measuring optical density per unit area. The left soleus muscles were used for quantifying Piezo1, PGC-1α, MFN-1 mRNA expression, and mitochondrial DNA (mtDNA).
The ROM of ankle joint dorsiflexion, optical density of NADH-TR and SDH staining, Piezo1, PGC-1α, MFN-1 mRNA expression, and mtDNA in the immobilization group were significantly lower than those in the control group at each time point.
In immobilized skeletal muscles, the Piezo1/PGC-1α/MFN-1 pathway inactivation caused mitochondrial dysfunction, which may induce myonuclear apoptosis via the cleaved caspase-3 upregulation. These changes may induce IL-1β/TGF-β1 pathway activation triggered by macrophage accumulation, leading to fibrosis and eventually to muscle contracture induced limited ROM.
This study was basic animal research aimed at elucidating the developmental mechanism of muscle contracture, a target of physiotherapy. The findings of this research are meaningful for physiotherapy because they provide basic medical data for creating new intervention strategies for muscle contractures and ultimately limited ROM.
Muscle contracture
Mitochondrial dysfunction
