Acceleration of Skeletal Muscle Regeneration in a Rat Skeletal Muscle Injury Model by Local Injection of Human Peripheral Blood-Derived CD133-Positive Cells

Abstract Background Pressure ulcers (PUs) are a major clinical problem that constitutes a tremendous economic burden on healthcare systems. Deep tissue injury (DTI) is a unique serious type of pressure ulcer that arises in skeletal muscle tissue. DTI arises in part because skeletal muscle tissues are more susceptible than skin to external compression. Unfortunately, few effective therapies are currently available for muscle injury. Basic fibroblast growth factor (bFGF), a potent mitogen and survival factor for various cells, plays a crucial role in the regulation of muscle development and homeostasis. The main purpose of this study was to test whether local administration of bFGF could accelerate muscle regeneration in a rat DTI model. Methods Male Sprague Dawley (SD) rats (age 12 weeks) were individually housed in plastic cages and a DTI PU model was induced according to methods described before. Animals were randomly divided into three groups: a normal group, a PU group treated with saline, and a PU group treated with bFGF (10 μg/0.1 ml) subcutaneously near the wound. Results We found that application of bFGF accelerated the rate of wound closure and promoted cell proliferation and tissue angiogenesis. In addition, compared to saline administration, bFGF treatment prevented collagen deposition, a measure of fibrosis, and up-regulated the myogenic marker proteins MyHC and myogenin, suggesting bFGF promoted injured muscle regeneration. Moreover, bFGF treatment increased levels of myogenesis-related proteins p-Akt and p-mTOR. Conclusions Our findings show that bFGF accelerated injured skeletal muscle regeneration through activation of the PI3K/Akt/mTOR signaling pathway and suggest that administration of bFGF is a potential therapeutic strategy for the treatment of skeletal muscle injury in PUs.

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Downregulated miR-204 Promotes Skeletal Muscle Regeneration

BioMed Research International ◽

10.1155/2020/3183296 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Ya Tan ◽

Linyuan Shen ◽

Mailin Gan ◽

Yuan Fan ◽

Xiao Cheng ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Regeneration ◽

Muscle Injury ◽

Target Genes ◽

C2c12 Cell ◽

Skeletal Muscle Regeneration ◽

Luciferase Reporter ◽

Limited Information ◽

Reporter System ◽

Skeletal Muscle Injury

Skeletal muscle is the most abundant and a highly plastic tissue of the mammals, especially when it comes to regenerate after trauma, but there is limited information about the mechanism of muscle repair and its regeneration. In the present study, we found that miR-204 is downregulated after skeletal muscle injury. In vitro experiments showed that over-expression of miR-204 by transfecting with miR-204 mimics suppressed C2C12 cell proliferation, migration, and blocked subsequent differentiation, whereas inhibition of miR-204 by transfecting with miR-204 inhibitor showed the converse effects. Furthermore, through the dual luciferase reporter system, we demonstrated that miR-204 can target the 3’UTR regions of Pax7, IGF1, and Mef2c and inhibit their expression. Taken together, our results suggest that Pax7, IGF1, and Mef2c are the target genes of miR-204 in the process of myoblasts proliferation, cell migration, and differentiation, respectively, and may contribute to mouse skeletal muscle regeneration. Our results may provide new ideas and references for the skeletal muscle study and may also provide therapeutic strategies of skeletal muscle injury.

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A randomized placebo-controlled clinical trial of Nicotinamide Riboside and Pterostilbene supplementation in experimental muscle injury in elderly subjects

10.1101/2021.10.04.21264504 ◽

2021 ◽

Author(s):

Jonas Brorson Jensen ◽

Ole Lindgaard Dollerup ◽

Andreas Buch Moeller ◽

Tine Borum Billeskov ◽

Emilie Dalbram ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Regeneration ◽

Muscle Injury ◽

Skeletal Muscle Regeneration ◽

Elderly Subjects ◽

Controlled Clinical Trial ◽

Post Injury ◽

Skeletal Muscle Injury ◽

Nicotinamide Riboside ◽

Muscle Work

Background Maintenance and regeneration of functional skeletal muscle are dependent on a sufficient pool of muscle stem cells (MuSCs). During ageing there is a functional decline in this cellular pool which influences the regenerative capacity of skeletal muscle. Preclinical evidence have suggested that Nicotinamide Riboside (NR) and Pterostilbene (PT) can improve muscle regeneration e.g. by increasing MuSC function. The objective of the present study was to investigate if NRPT supplementation promotes skeletal muscle regeneration after muscle injury in elderly humans by improved recruitment of MuSCs. Methods In a randomized, double-blinded, placebo-controlled trial, 32 elderly men and women (55-80 yr) received daily supplementation with either NRPT (1000 mg NR + 200 mg PT) or matched placebo. Two weeks after initiation of supplementation, a skeletal muscle injury was applied in the vastus lateralis part of the quadriceps femoris muscle by electrically induced eccentric muscle work in a dynamometer. Skeletal muscle biopsies were obtained pre, 2h, 2, 8, and 30 days post injury. The main outcome of the study was change in MuSC content 8 days post injury. Results 31 enrolled subjects completed the entire protocol. The muscle work induced a substantial skeletal muscle injury in the study participants and was associated with release of myoglobin and creatine kinase, muscle soreness, tissue edema, and a decrease in muscle strength. MuSC content increased by 107% 8 days post injury (p= 0.0002) but with no effect of NRPT supplementation (p=0.58 for supplementation effect). MuSC proliferation and cell size revealed a large demand for recruitment post injury but was not affected by NRPT. Furthermore, histological analyses of muscle fiber area, internal nuclei and embryonic Myosin Heavy Chain showed no effect of NRPT supplementation. Conclusion Daily supplementation with 1000 mg NR + 200 mg PT is safe but does not improve recruitment of the MuSC pool or other measures of muscle recovery in response to injury or subsequent regeneration in elderly subjects.

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Pim1 kinase positively regulates myoblast behaviors and skeletal muscle regeneration

Cell Death and Disease ◽

10.1038/s41419-019-1993-3 ◽

2019 ◽

Vol 10 (10) ◽

Cited By ~ 1

Author(s):

Yuantong Liu ◽

Yue Shang ◽

Zihan Yan ◽

Hao Li ◽

Zhen Wang ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Regeneration ◽

Muscle Injury ◽

Myogenic Differentiation ◽

Skeletal Muscle Regeneration ◽

Myoblast Differentiation ◽

Adult Skeletal Muscle ◽

Skeletal Muscle Injury ◽

Pim1 Kinase

Abstract Adult skeletal muscle regeneration after injury depends on normal myoblast function. However, the intrinsic mechanisms for the control of myoblast behaviors are not well defined. Herein, we identified Pim1 kinase as a novel positive regulator of myoblast behaviors in vitro and muscle regeneration in vivo. Specifically, knockdown of Pim1 significantly restrains the proliferation and accelerates the apoptosis of myoblasts in vitro, indicating that Pim1 is critical for myoblast survival and amplification. Meanwhile, we found that Pim1 kinase is increased and translocated from cytoplasm into nucleus during myogenic differentiation. By using Pim1 kinase inhibitor, we proved that inhibition of Pim1 activity prevents myoblast differentiation and fusion, suggesting the necessity of Pim1 kinase activity for proper myogenesis. Mechanistic studies demonstrated that Pim1 kinase interacts with myogenic regulator MyoD and controls its transcriptional activity, inducing the expression of muscle-specific genes, which consequently promotes myogenic differentiation. Additionally, in skeletal muscle injury mouse model, deletion of Pim1 hinders the regeneration of muscle fibers and the recovery of muscle strength. Taken together, our study provides a potential target for the manipulation of myoblast behaviors in vitro and the myoblast-based therapeutics of skeletal muscle injury.

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