Enhancement of mitochondrial energy metabolism by melatonin promotes vascularized skeletal muscle regeneration in a volumetric muscle loss model

Nov 26, 2023Free radical biology & medicine

Melatonin boosts muscle energy production to improve blood vessel growth and muscle repair after large injuries

AI simplified

Regenerative Health on OpenScience ↗PubMed ↗DOI ↗

Abstract

In vitro administration of melatonin significantly enhanced myogenesis in C2C12 myoblast cells in a dose-dependent manner.

Melatonin is associated with improved myoblast differentiation and recovery of skeletal muscle following volumetric muscle loss (VML).
The up-regulation of myogenic marker genes indicates enhanced muscle formation due to melatonin treatment.
SIRT3 plays a critical role in melatonin's ability to promote myoblast differentiation by enhancing mitochondrial energy metabolism.
Silencing of SIRT3 negates the protective effects of melatonin on myoblast mitochondrial function, resulting in increased oxidative stress and reduced ATP production.
Implantation of liposome-encapsulated melatonin in a hydrogel stimulates myofiber formation and new blood vessel development in muscle defects.

AI simplified

Volumetric muscle loss (VML) is a condition that results in the extensive loss of 20 % or more of skeletal muscle due to trauma or tumor ablation, leading to severe functional impairment and permanent disability. The current surgical interventions have limited functional regeneration of skeletal muscle due to the compromised self-repair mechanism. Melatonin has been reported to protect skeletal muscle from exercise-induced oxidative damage and holds great potential to treat muscle diseases. In this study, we hypothesize that melatonin can enhance myoblast differentiation and promote effective recovery of skeletal muscle following VML. In vitro administration of melatonin resulted in a significant enhancement of myogenesis in C2C12 myoblast cells, as evidenced by the up-regulation of myogenic marker genes in a dose-dependent manner. Further experiments revealed that silent information of regulator type 3 (SIRT3) played a critical role in the melatonin-enhanced myoblast differentiation through enhancement of mitochondrial energy metabolism and activation of mitochondrial antioxidant enzymes such as superoxide dismutase 2 (SOD2). Silencing of Sirt3 completely abrogated the protective effect of melatonin on the mitochondrial function of myoblasts, evidenced by the increased reactive oxygen species, decreased adenosine triphosphate production, and down-regulated myoblast-specific marker gene expression. In order to attain a protracted and consistent release, liposome-encapsuled melatonin was integrated into gelatin methacryloyl hydrogel (GelMA-Lipo@MT). The implantation of GelMA-Lipo@MT into a tibialis anterior muscle defect in a VML model effectively stimulated the formation of myofibers and new blood vessels in situ, while concurrently inhibiting fibrotic collagen deposition. The findings of this study indicate that the incorporation of melatonin with GelMA hydrogel has facilitated the de novo vascularized skeletal muscle regeneration by augmenting mitochondrial energy metabolism. This represents a promising approach for the development of skeletal muscle tissue engineering, which could be utilized for the treatment of VML and other severe muscle injuries.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Enhancement of mitochondrial energy metabolism by melatonin promotes vascularized skeletal muscle regeneration in a volumetric muscle loss model

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week: