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 Necdin mediates skeletal muscle regeneration by promoting myoblast survival and differentiation

2007 ◽  
Vol 179 (2) ◽  
pp. 305-319 ◽  
Author(s):  
Daniela Deponti ◽  
Stéphanie François ◽  
Silvia Baesso ◽  
Clara Sciorati ◽  
Anna Innocenzi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transgenic Mice ◽  
Satellite Cell ◽  
Muscle Regeneration ◽  
Muscle Injury ◽  
Muscle Fibers ◽  
Skeletal Muscle Regeneration ◽  
Muscle Degeneration ◽  
Wild Type ◽  
Cell Type

Regeneration of muscle fibers that are lost during pathological muscle degeneration or after injuries is sustained by the production of new myofibers. An important cell type involved in muscle regeneration is the satellite cell. Necdin is a protein expressed in satellite cell–derived myogenic precursors during perinatal growth. However, its function in myogenesis is not known. We compare transgenic mice that overexpress necdin in skeletal muscle with both wild-type and necdin null mice. After muscle injury the necdin null mice show a considerable defect in muscle healing, whereas mice that overexpress necdin show a substantial increase in myofiber regeneration. We also find that in muscle, necdin increases myogenin expression, accelerates differentiation, and counteracts myoblast apoptosis. Collectively, these data clarify the function and mechanism of necdin in skeletal muscle and show the importance of necdin in muscle regeneration.

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.

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 Thyroid Hormone Receptor Alpha is Essential to Maintain the Satellite Cell Niche During Skeletal Muscle Injury and Sarcopenia of Aging

Thyroid ◽  
2017 ◽  
Vol 27 (10) ◽  
pp. 1316-1322 ◽  
Author(s):  
Anna Milanesi ◽  
Jang-Won Lee ◽  
An Yang ◽  
Yan-Yun Liu ◽  
Sargis Sedrakyan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
Satellite Cell ◽  
Hormone Receptor ◽  
Muscle Injury ◽  
Thyroid Hormone Receptor ◽  
Skeletal Muscle Injury ◽  
Receptor Alpha ◽  
Satellite Cell Niche ◽  
Cell Niche

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 Loss of the adipokine lipocalin-2 impairs satellite cell activation and skeletal muscle regeneration

2018 ◽  
Vol 315 (5) ◽  
pp. C714-C721 ◽  
Author(s):  
Irena A. Rebalka ◽  
Cynthia M. F. Monaco ◽  
Nina E. Varah ◽  
Thorsten Berger ◽  
Donna M. D’souza ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Cell Activation ◽  
Skeletal Muscle Regeneration ◽  
Matrix Remodeling ◽  
Muscle Repair ◽  
Lipocalin 2 ◽  
The Impact

Lipocalin-2 (LCN2) is an adipokine previously described for its contribution to numerous processes, including innate immunity and energy metabolism. LCN2 has also been demonstrated to be an extracellular matrix (ECM) regulator through its association with the ECM protease matrix metalloproteinase-9 (MMP-9). With the global rise in obesity and the associated comorbidities related to increasing adiposity, it is imperative to gain an understanding of the cross talk between adipose tissue and other metabolic tissues, such as skeletal muscle. Given the function of LCN2 on the ECM in other tissues and the importance of matrix remodeling in skeletal muscle regeneration, we examined the localization and expression of LCN2 in uninjured and regenerating wild-type skeletal muscle and assessed the impact of LCN2 deletion (LCN2−/−) on skeletal muscle repair following cardiotoxin injury. Though LCN2 was minimally present in uninjured skeletal muscle, its expression was increased significantly at 1 and 2 days postinjury, with expression present in Pax7-positive satellite cells. Although satellite cell content was unchanged, the ability of quiescent satellite cells to become activated was significantly impaired in LCN2−/− skeletal muscles. Skeletal muscle regeneration was also significantly compromised as evidenced by decreased embryonic myosin heavy chain expression and smaller regenerating myofiber areas. Consistent with a role for LCN2 in MMP-9 regulation, regenerating muscle also displayed a significant increase in fibrosis and lower ( P = 0.07) MMP-9 activity in LCN2−/− mice at 2 days postinjury. These data highlight a novel role for LCN2 in muscle regeneration and suggest that changes in adipokine expression can significantly impact skeletal muscle repair.

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