Macrophages and skeletal muscle regeneration: a clodronate-containing liposome depletion study

2006 ◽  
Vol 290 (6) ◽  
pp. R1488-R1495 ◽  
Author(s):  
Mukesh Summan ◽  
Gordon L. Warren ◽  
Robert R. Mercer ◽  
Rebecca Chapman ◽  
Tracy Hulderman ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Injury ◽  
High Mobility ◽  
Repair Process ◽  
Skeletal Muscle Regeneration ◽  
Skeletal Muscle Injury ◽  
Clodronate Liposome ◽  
Liposomal Clodronate ◽  
Peripheral Monocyte ◽  
Myogenic Factors

The study evaluates the influence of monocytes/macrophages in the mechanisms of skeletal muscle injury using a mouse model and selective depletion of peripheral monocyte with systemic injections of liposomal clodronate (dichloromethylene bisphosphonate). This pharmacological treatment has been demonstrated to induce specific apoptotic death in monocytes and phagocytic macrophages. In the current studies, the liposomal clodronate injections resulted in a marked attenuation of the peak inflammatory response in the freeze-injured muscle in the first three days after injury. The effect was accompanied by a transient reduction (at day 1 or 3 postinjury) of the expression of several genes coding for inflammatory, as well as growth-related mediators, including TNF, monocyte chemoattractant protein (MCP)-1, thioredoxin, high-mobility group AT-hook 1, insulin-like growth factor-binding protein (IGFBP), and IGF-1. In contrast, the expression of major myogenic factors (i.e., MyoD and myogenin) directly involved in the activation/proliferation and differentiation of muscle precursor cells was not altered by the clodronate liposome treatment. The repair process in the injured muscle of clodronate liposome-treated mice was characterized by prolonged clearance of necrotic myofibers and a tendency for increased muscle fat accumulation at day 9 and 14 postinjury, respectively. In conclusion, a significant reduction of the initial monocyte/macrophage influx into the injured muscle is associated with not improved, but moderately impaired, repair processes after skeletal muscle injury.

scholarly journals Morphological evidence for telocytes as stromal cells supporting satellite cell activation in eccentric contraction-induced skeletal muscle injury

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mirko Manetti ◽  
Alessia Tani ◽  
Irene Rosa ◽  
Flaminia Chellini ◽  
Roberta Squecco ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Muscle Injury ◽  
Cell Activation ◽  
Tissue Injury ◽  
Ex Vivo ◽  
Eccentric Contraction ◽  
Skeletal Muscle Regeneration ◽  
Morphological Evidence ◽  
Skeletal Muscle Injury

Abstract Although telocytes (TCs) have been proposed to play a “nursing” role in resident satellite cell (SC)-mediated skeletal muscle regeneration, currently there is no evidence of TC-SC morpho-functional interaction following tissue injury. Hence, we explored the presence of TCs and their relationship with SCs in an ex vivo model of eccentric contraction (EC)-induced muscle damage. EC-injured muscles showed structural/ultrastructural alterations and changes in electrophysiological sarcolemnic properties. TCs were identified in control and EC-injured muscles by either confocal immunofluorescence (i.e. CD34+CD31− TCs) or transmission electron microscopy (TEM). In EC-injured muscles, an extended interstitial network of CD34+ TCs/telopodes was detected around activated SCs displaying Pax7+ and MyoD+ nuclei. TEM revealed that TCs invaded the SC niche passing with their telopodes through a fragmented basal lamina and contacting the underlying activated SCs. TC-SC interaction after injury was confirmed in vitro by culturing single endomysial sheath-covered myofibers and sprouting TCs and SCs. EC-damaged muscle-derived TCs showed increased expression of the recognized pro-myogenic vascular endothelial growth factor-A, and SCs from the same samples exhibited increased MyoD expression and greater tendency to fuse into myotubes. Here, we provide the essential groundwork for further investigation of TC-SC interactions in the setting of skeletal muscle injury and regenerative medicine.

scholarly journals Myoprotective effects of bFGF on skeletal muscle injury in pressure-related deep tissue injury in rats

2016 ◽  
Vol 4 ◽  
pp. 1-10 ◽  
Author(s):  
Hongxue Shi ◽  
Haohuang Xie ◽  
Yan Zhao ◽  
Cai Lin ◽  
Feifei Cui ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Muscle Injury ◽  
Muscle Development ◽  
Tissue Injury ◽  
Skeletal Muscle Regeneration ◽  
Deep Tissue ◽  
External Compression ◽  
Deep Tissue Injury ◽  
Skeletal Muscle Injury

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.

scholarly journals Downregulated miR-204 Promotes Skeletal Muscle Regeneration

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.

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

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.

scholarly journals Pim1 kinase positively regulates myoblast behaviors and skeletal muscle regeneration

2019 ◽  
Vol 10 (10) ◽  
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.

scholarly journals Assessment of Preclinical Liver and Skeletal Muscle Biomarkers Following Clofibrate Administration in Wistar Rats

2017 ◽  
Vol 45 (4) ◽  
pp. 506-525 ◽  
Author(s):  
Pierre Maliver ◽  
Matthias Festag ◽  
Moritz Bennecke ◽  
Francois Christen ◽  
Balázs Bánfai ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Injury ◽  
Wistar Rats ◽  
Liver Toxicity ◽  
High Mobility ◽  
Type I ◽  
Fatty Acid Binding ◽  
Toxic Dose ◽  
Skeletal Muscle Injury ◽  
Arginase 1

Clofibrate is a known rodent hepatotoxicant classically associated with hepatocellular hypertrophy and increased serum activities of cellular alanine aminotransferase/aspartate aminotransferase (ALT/AST) in the absence of microscopic hepatocellular degeneration. At toxic dose, clofibrate induces liver and skeletal muscle injury. The objective of this study was to assess novel liver and skeletal muscle biomarkers following clofibrate administration in Wistar rats at different dose levels for 7 days. In addition to classical biomarkers, liver injury was assessed by cytokeratin 18 (CK18) cleaved form, high-mobility group box 1, arginase 1 (ARG1), microRNA 122 (miR-122), and glutamate dehydrogenase. Skeletal muscle injury was evaluated with fatty acid binding protein 3 (Fabp3) and myosin light chain 3 (Myl3). Clofibrate-induced hepatocellular hypertrophy and skeletal muscle degeneration (type I rich muscles) were noted microscopically. CK, Fabp3, and Myl3 elevations correlated to myofiber degeneration. Fabp3 and Myl3 outperformed CK for detection of myofiber degeneration of minimal severity. miR-122 and ARG1 results were significantly correlated and indicated the absence of liver toxicity at low doses of clofibrate, despite increased ALT/AST activities. Moreover, combining classical and novel biomarkers (Fabp3, Myl3, ARG1, and miR-122) can be considered a valuable strategy for differentiating increased transaminases due to liver toxicity from skeletal muscle toxicity.

scholarly journals Stem Cells for the Treatment of Skeletal Muscle Injury

2009 ◽  
Vol 28 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Andres J. Quintero ◽  
Vonda J. Wright ◽  
Freddie H. Fu ◽  
Johnny Huard
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Muscle Injury ◽  
Skeletal Muscle Injury

scholarly journals Modelling the skeletal muscle injury recovery using in vivo contrast-enhanced micro-CT: a proof-of-concept study in a rat model

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Bruno Paun ◽  
Daniel García Leon ◽  
Alex Claveria Cabello ◽  
Roso Mares Pages ◽  
Elena de la Calle Vargas ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Rat Model ◽  
Muscle Injury ◽  
Micro Ct ◽  
Skeletal Muscle Injury ◽  
Monitoring Time ◽  
Contrast Enhanced Ct ◽  
Contrast Enhanced ◽  
Injury Recovery

Abstract Background Skeletal muscle injury characterisation during healing supports trauma prognosis. Given the potential interest of computed tomography (CT) in muscle diseases and lack of in vivo CT methodology to image skeletal muscle wound healing, we tracked skeletal muscle injury recovery using in vivo micro-CT in a rat model to obtain a predictive model. Methods Skeletal muscle injury was performed in 23 rats. Twenty animals were sorted into five groups to image lesion recovery at 2, 4, 7, 10, or 14 days after injury using contrast-enhanced micro-CT. Injury volumes were quantified using a semiautomatic image processing, and these values were used to build a prediction model. The remaining 3 rats were imaged at all monitoring time points as validation. Predictions were compared with Bland-Altman analysis. Results Optimal contrast agent dose was found to be 20 mL/kg injected at 400 μL/min. Injury volumes showed a decreasing tendency from day 0 (32.3 ± 12.0mm3, mean ± standard deviation) to day 2, 4, 7, 10, and 14 after injury (19.6 ± 12.6, 11.0 ± 6.7, 8.2 ± 7.7, 5.7 ± 3.9, and 4.5 ± 4.8 mm3, respectively). Groups with single monitoring time point did not yield significant differences with the validation group lesions. Further exponential model training with single follow-up data (R2 = 0.968) to predict injury recovery in the validation cohort gave a predictions root mean squared error of 6.8 ± 5.4 mm3. Further prediction analysis yielded a bias of 2.327. Conclusion Contrast-enhanced CT allowed in vivo tracking of skeletal muscle injury recovery in rat.

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