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

被引:3
|
作者
Ge, Xiaoyang [1 ,2 ]
Wang, Chengyue [1 ,2 ]
Yang, Guanyu [1 ,2 ]
Maimaiti, Dimulati [2 ,3 ,4 ]
Hou, Mingzhuang [1 ,2 ]
Liu, Hao [1 ,2 ]
Yang, Huilin [1 ,2 ]
Chen, Xi [3 ,4 ]
Xu, Yong [1 ,2 ,5 ]
He, Fan [1 ,2 ,5 ]
机构
[1] Soochow Univ, Affiliated Hosp 1, Dept Orthopaed, Suzhou 215006, Peoples R China
[2] Soochow Univ, Suzhou Med Coll, Orthopaed Inst, Suzhou 215007, Peoples R China
[3] Soochow Univ, Sch Biol & Basic Med Sci, Suzhou Med Coll, Suzhou 215123, Peoples R China
[4] Soochow Univ, Affiliated Hosp 3, Dept Pathol, 185 Juqian Rd, Changzhou 213003, Jiangsu, Peoples R China
[5] Soochow Univ, Orthopaed Inst, Med Coll, 178 East Ganjiang Rd, Suzhou 215000, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Melatonin; Skeletal muscle; Volumetric muscle loss; Mitochondrial energy metabolism; SIRT3; GELATIN METHACRYLOYL GELMA; EXPRESSION; PROTEIN; PATHWAY; SOD2;
D O I
10.1016/j.freeradbiomed.2023.11.021
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 upregulation 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.
引用
收藏
页码:146 / 157
页数:12
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