scholarly journals Ibuprofen does not Impair Skeletal Muscle Regeneration Upon Cardiotoxin-Induced Injury

2020 ◽  
pp. 847-859
Author(s):  
S DALLE ◽  
C POFFÉ ◽  
C HIROUX ◽  
F SUHR ◽  
L DELDICQUE ◽  
...  
Keyword(s):  
Immune Cells ◽  
Muscle Regeneration ◽  
Tibialis Anterior ◽  
Skeletal Muscle Regeneration ◽  
Muscle Recovery ◽  
Inflammatory Signaling ◽  
Nsaid Treatment ◽  
Transient Improvement ◽  
Cox 2 ◽  
Muscle Fiber Regeneration

Muscle regeneration is regulated through interaction between muscle and immune cells. Studies showed that treatment with supra-physiological doses of Non-Steroidal Anti-Inflammatory Drug (NSAID) abolished inflammatory signaling and impaired muscle recovery. The present study examines the effects of pharmacologically-relevant NSAID treatment on muscle regeneration. C57BL/6 mice were injected in the tibialis anterior (TA) with either PBS or cardiotoxin (CTX). CTX-injected mice received ibuprofen (CTX-IBU) or were untreated (CTX-PLAC). After 2 days, Il-1β and Il-6 expression was upregulated in the TA of CTX-IBU and CTX-PL vs. PBS. However, Cox-2 expression and macrophage infiltration were higher in CTX-PL vs. PBS, but not in CTX-IBU. At the same time, anabolic markers were higher in CTX-IBU vs. PBS, but not in CTX-PL. Nevertheless, ibuprofen did not affect muscle mass or muscle fiber regeneration. In conclusion, mild ibuprofen doses did not worsen muscle regeneration. There were even signs of a transient improvement in anabolic signaling and attenuation of inflammatory signaling.

scholarly journals Improvement of Skeletal Muscle Regeneration by Platelet-Rich Plasma in Rats with Experimental Chronic Hyperglycemia

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Raed Rtail ◽  
Olena Maksymova ◽  
Viacheslav Illiashenko ◽  
Olena Gortynska ◽  
Oleksii Korenkov ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Connective Tissue ◽  
Muscle Regeneration ◽  
Platelet Rich Plasma ◽  
Triceps Surae ◽  
Skeletal Muscle Regeneration ◽  
Male Rats ◽  
Tissue Development ◽  
Muscle Recovery ◽  
Chronic Hyperglycemia

Herein, the structural effect of autologous platelet-rich plasma (PRP) on posttraumatic skeletal muscle regeneration in rats with chronic hyperglycemia (CH) was tested. 130 white laboratory male rats divided into four groups (I—control; II—rats with CH; III—rats with CH and PRP treatment; and IV—rats for CH confirmation) were used for the experiment. CH was simulated by streptozotocin and nicotinic acid administration. Triceps surae muscle injury was reproduced by transverse linear incision. Autologous PRP was used in order to correct the possible negative CH effect on skeletal muscle recovery. On the 28th day after the injury, the regenerating muscle fiber and blood vessel number in the CH+PRP group were higher than those in the CH rats. However, the connective tissue area in the CH group was larger than that in the CH+PRP animals. The amount of agranulocytes in the regenerating muscle of the CH rats was lower compared to that of the CH+PRP group. The histological analysis of skeletal muscle recovery in CH+PRP animals revealed more intensive neoangiogenesis compared to that in the CH group. Herewith, the massive connective tissue development and inflammation signs were observed within the skeletal muscle of CH rats. Obtained results suggest that streptozotocin-induced CH has a negative effect on posttraumatic skeletal muscle regeneration, contributing to massive connective tissue development. The autologous PRP injection promotes muscle recovery process in rats with CH, shifting it away from fibrosis toward the complete muscular organ repair.

scholarly journals Evaluation of skeletal muscle regeneration in experimental model after malnutrition

2017 ◽  
Vol 77 (1) ◽  
pp. 83-91 ◽  
Author(s):  
A. Pertille ◽  
K. F. Moura ◽  
C. Y. Matsumura ◽  
R. Ferretti ◽  
D. M. Ramos ◽  
...  
Keyword(s):  
Muscle Regeneration ◽  
Tibialis Anterior ◽  
Tibialis Anterior Muscle ◽  
Recovery Period ◽  
Protein Diet ◽  
Skeletal Muscle Regeneration ◽  
Post Injury ◽  
Cross Sectional ◽  
Young Rats ◽  
Normal Protein Diet

Abstract The aim of this study was to analyze muscle regeneration after cryoinjury in the tibialis anterior muscle of young rats that were malnourished and then recovered. Forty Wistar rats were divided into a nourished group that received a normal protein diet (14% casein) for 90 days and a malnourished and recovered rats group (MR) that was submitted to 45 days of malnutrition with a hypoproteic diet (6% casein) followed by 45 days of a normal protein diet (14% casein). After the recovery period, all of the animals underwent cryoinjury in the right tibialis anterior muscle and euthanasia after 7, 14 and 21 days. The amount of connective tissue and the inflammation area was higher in the malnutrition recovered injury MR group (MRI) at 14 days post-injury (p < 0.05). Additionally, the cross-sectional area (CSA) of the regenerated fibers was decreased in the MRI (p < 0.05). The MyoD and myogenin protein levels were higher in the nourished injury group. Similar levels of TGF-β1 were found between groups. The proposed malnutrition protocol was effective in showing delayed changes in the regeneration process of the tibialis anterior muscle of young rats. Furthermore, we observed a delay in muscle repair even after nutritional recovery.

scholarly journals The COX-2 pathway is essential during early stages of skeletal muscle regeneration

2004 ◽  
Vol 287 (2) ◽  
pp. C475-C483 ◽  
Author(s):  
Brenda A. Bondesen ◽  
Stephen T. Mills ◽  
Kristy M. Kegley ◽  
Grace K. Pavlath
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Inflammatory Cells ◽  
Skeletal Muscle Regeneration ◽  
Cellular Processes ◽  
Early Stages ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory

Skeletal muscle regeneration comprises several overlapping cellular processes, including inflammation and myogenesis. Prostaglandins (PGs) may regulate muscle regeneration, because they modulate inflammation and are involved in various stages of myogenesis in vitro. PG synthesis is catalyzed by different isoforms of cyclooxygenase (COX), which are inhibited by nonsteroidal anti-inflammatory drugs. Although experiments employing nonsteroidal anti-inflammatory drugs have implicated PGs in tissue repair, how PGs regulate muscle regeneration remains unclear, and the potentially distinct roles of different COX isoforms have not been investigated. To address these questions, a localized freeze injury was induced in the tibialis anterior muscles of mice chronically treated with either a COX-1- or COX-2-selective inhibitor (SC-560 and SC-236, respectively), starting before injury. The size of regenerating myofibers was analyzed at time points up to 5 wk after injury and found to be decreased by SC-236 and in COX-2−/− muscles, but unaffected by SC-560. In contrast, SC-236 had no effect on myofiber growth when administered starting 7 days after injury. The attenuation of myofiber growth by SC-236 treatment and in COX-2−/− muscles is associated with decreases in the number of myoblasts and intramuscular inflammatory cells at early times after injury. Together, these data suggest that COX-2-dependent PG synthesis is required during early stages of muscle regeneration and thus raise caution about the use of COX-2-selective inhibitors in patients with muscle injury or disease.

scholarly journals Septin-7 is indispensable in skeletal muscle regeneration

2021 ◽  
Vol 154 (9) ◽  
Author(s):  
Andrea Telek ◽  
Janos Fodor ◽  
Nora Dobrosi ◽  
Laszlo Szabo ◽  
Monika Gönczi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Division ◽  
Mrna Expression ◽  
Muscle Regeneration ◽  
Tibialis Anterior ◽  
Tibialis Anterior Muscle ◽  
Critical Role ◽  
Skeletal Muscle Regeneration ◽  
The Right

Septins are considered as the fourth component of the cytoskeleton, with septin-7 isoform playing a critical role in myogenic cell division and fusion. Skeletal muscle regeneration is a highly orchestrated process that requires many steps, including proper cell division to achieve functional recovery. Here, the role of septin-7 was investigated in this complex process. To this end, muscle injury was induced in wild type BL6/C57 and septin-7–conditional (mer-Cre-mer) knock-down mice by in vivo BaCl2 injection to the left m. tibialis anterior muscle (TA) of the mice (the right m. tibialis anterior muscle was nontreated control). Mice were sacrificed 4 and 14 d later to reflect the early (monitored by PAX7 level) and late (monitored by myogenin level) phases of muscle regeneration. Western blotting was used to follow the changes of septin-7, PAX7, and myogenin expression at the protein level, while changes of mRNA were detected by qPCR. Morphological differences were visualized by HE staining. Levels of septin-7 protein increased 4 and 14 d after injury in BL6/C57 mice and mRNA expression of SEPT7 showed significant elevation both 4 and 14 d after injection in Cre+ mice only, considered to be a compensatory increase of mRNA expression of SEPT7 in order to ensure the appropriate regeneration process. Furthermore, up-regulation of septin-7 protein was more pronounced on day 14 in both Cre− and Cre+ mice, which may indicate its importance in the later phase of regeneration. Level of PAX7 and myogenin were also increased 4 and 14 d after injury in BL6/C57, Cre−, and Cre+ mice, respectively. Taken together, our data suggest the importance of septin-7 in skeletal muscle regeneration.

scholarly journals IL-1β and TNF-α Modulation of Proliferated and Committed Myoblasts: IL-6 and COX-2-Derived Prostaglandins as Key Actors in the Mechanisms Involved

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2005
Author(s):  
Angela M. Alvarez ◽  
Carlos DeOcesano-Pereira ◽  
Catarina Teixeira ◽  
Vanessa Moreira
Keyword(s):  
Cell Proliferation ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration ◽  
Myoblast Differentiation ◽  
Tnf Α ◽  
Cox 2 ◽  
Myoblast Cells ◽  
Inflammatory Signalling ◽  
Mouse Myoblast

In this study, we investigated the effects and mechanisms of the pro-inflammatory cytokines IL-1β and TNF-α on the proliferation and commitment phases of myoblast differentiation. C2C12 mouse myoblast cells were cultured to reach a proliferated or committed status and were incubated with these cytokines for the evaluation of cell proliferation, cyclooxygenase 2 (COX-2) expression, release of prostaglandins (PGs) and myokines, and activation of myogenic regulatory factors (MRFs). We found that inhibition of the IL-6 receptor reduced IL-1β- and TNF-α-induced cell proliferation, and that the IL-1β effect also involved COX-2-derived PGs. Both cytokines modulated the release of the myokines myostatin, irisin, osteonectin, and IL-15. TNF-α and IL-6 reduced the activity of Pax7 in proliferated cells and reduced MyoD and myogenin activity at both proliferative and commitment stages. Otherwise, IL-1β increased myogenin activity only in committed cells. Our data reveal a key role of IL-6 and COX-2-derived PGs in IL-1β and TNF-α-induced myoblast proliferation and support the link between TNF-α and IL-6 and the activation of MRFs. We concluded that IL-1β and TNF-α induce similar effects at the initial stages of muscle regeneration but found critical differences between their effects with the progression of the process, bringing new insights into inflammatory signalling in skeletal muscle regeneration.

Inactivation of PPARβ/δ adversely affects satellite cells and reduces postnatal myogenesis

2015 ◽  
Vol 309 (2) ◽  
pp. E122-E131 ◽  
Author(s):  
Preeti Chandrashekar ◽  
Ravikumar Manickam ◽  
Xiaojia Ge ◽  
Sabeera Bonala ◽  
Craig McFarlane ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Tibialis Anterior ◽  
Tibialis Anterior Muscle ◽  
Skeletal Muscle Regeneration ◽  
Muscle Weight ◽  
Cross Sectional ◽  
Postnatal Myogenesis

Peroxisome proliferator-activated receptor β/δ ( PPARβ/δ) is a ubiquitously expressed gene with higher levels observed in skeletal muscle. Recently, our laboratory showed (Bonala S, Lokireddy S, Arigela H, Teng S, Wahli W, Sharma M, McFarlane C, Kambadur R. J Biol Chem 287: 12935–12951, 2012) that PPARβ/δ modulates myostatin activity to induce myogenesis in skeletal muscle. In the present study, we show that PPARβ/δ-null mice display reduced body weight, skeletal muscle weight, and myofiber atrophy during postnatal development. In addition, a significant reduction in satellite cell number was observed in PPARβ/δ-null mice, suggesting a role for PPARβ/δ in muscle regeneration. To investigate this, tibialis anterior muscles were injured with notexin, and muscle regeneration was monitored on days 3, 5, 7, and 28 postinjury. Immunohistochemical analysis revealed an increased inflammatory response and reduced myoblast proliferation in regenerating muscle from PPARβ/δ-null mice. Histological analysis confirmed that the regenerated muscle fibers of PPARβ/δ-null mice maintained an atrophy phenotype with reduced numbers of centrally placed nuclei. Even though satellite cell numbers were reduced before injury, satellite cell self-renewal was found to be unaffected in PPARβ/δ-null mice after regeneration. Previously, our laboratory had showed (Bonala S, Lokireddy S, Arigela H, Teng S, Wahli W, Sharma M, McFarlane C, Kambadur R. J Biol Chem 287: 12935–12951, 2012) that inactivation of PPARβ/δ increases myostatin signaling and inhibits myogenesis. Our results here indeed confirm that inactivation of myostatin signaling rescues the atrophy phenotype and improves muscle fiber cross-sectional area in both uninjured and regenerated tibialis anterior muscle from PPARβ/δ-null mice. Taken together, these data suggest that absence of PPARβ/δ leads to loss of satellite cells, impaired skeletal muscle regeneration, and postnatal myogenesis. Furthermore, our results also demonstrate that functional antagonism of myostatin has utility in rescuing these effects.

scholarly journals A tale of two niches: differential functions for VCAM-1 in satellite cells under basal and injured conditions

2017 ◽  
Vol 313 (4) ◽  
pp. C392-C404 ◽  
Author(s):  
Hyo-Jung Choo ◽  
James P. Canner ◽  
Katherine E. Vest ◽  
Zachary Thompson ◽  
Grace K. Pavlath
Keyword(s):  
Stem Cells ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Satellite Cells ◽  
Immune Cells ◽  
Muscle Regeneration ◽  
Cell Types ◽  
Skeletal Muscle Regeneration ◽  
Phosphorylated Akt ◽  
Cell Cell

Cell-cell adhesion molecules play key roles in maintaining quiescence or promoting activation of various stem cells in their niche. Muscle stem cells called satellite cells (SC) are critical for skeletal muscle regeneration after injury, but little is known about the role of adhesion molecules in regulating the behavior of these stem cells. Vascular cell adhesion molecule-1 (VCAM-1) is a cell-cell adhesion protein expressed on quiescent and activated SC whose function is unknown in this context. We deleted Vcam1 from SC using an inducible Cre recombinase in young mice. In the injured niche, Vcam1−/−SC underwent premature lineage progression to a more differentiated state as well as apoptosis leading to a transient delay in myofiber growth during regeneration. Apoptosis was also increased in Vcam1−/−SC in vitro concomitant with decreased levels of phosphorylated Akt, a prosurvival signal activated by VCAM-1 signaling in other cell types. During muscle regeneration, we observed an influx of immune cells expressing α4 integrin, a component of the major, high-affinity VCAM-1 ligand, α4β1 integrin. Furthermore, α4 integrin mRNA and protein were induced in SC 2 days after injury. These results suggest that SC interact with other SC as well as immune cells through α4β1 integrin in the injured niche to promote expansion of SC. In the uninjured niche, multiple cell types also expressed α4 integrin. However, only basal fusion of Vcam1−/−SC with myofibers was decreased, contributing to decreased myofiber growth. These studies define differential roles for VCAM-1 in SC depending on the state of their niche.

scholarly journals The Role of Innate and Adaptive Immune Cells in Skeletal Muscle Regeneration

2021 ◽  
Vol 22 (6) ◽  
pp. 3265
Author(s):  
Natalia Ziemkiewicz ◽  
Genevieve Hilliard ◽  
Nicholas A. Pullen ◽  
Koyal Garg
Keyword(s):  
Skeletal Muscle ◽  
Immune Cells ◽  
Muscle Regeneration ◽  
Therapeutic Strategies ◽  
Skeletal Muscle Regeneration ◽  
Degenerative Diseases ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Complex Process

Skeletal muscle regeneration is highly dependent on the inflammatory response. A wide variety of innate and adaptive immune cells orchestrate the complex process of muscle repair. This review provides information about the various types of immune cells and biomolecules that have been shown to mediate muscle regeneration following injury and degenerative diseases. Recently developed cell and drug-based immunomodulatory strategies are highlighted. An improved understanding of the immune response to injured and diseased skeletal muscle will be essential for the development of therapeutic strategies.

scholarly journals Skeletal muscle regeneration in facioscapulohumeral muscular dystrophy is correlated with pathological severity

2020 ◽  
Vol 29 (16) ◽  
pp. 2746-2760 ◽  
Author(s):  
Christopher R S Banerji ◽  
Don Henderson ◽  
Rabi N Tawil ◽  
Peter S Zammit
Keyword(s):  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Muscle Regeneration ◽  
Tibialis Anterior ◽  
Myogenic Differentiation ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Skeletal Muscle Regeneration ◽  
Myotonic Dystrophy Type 2 ◽  
Regenerative Response ◽  
Muscle Biopsies

Abstract Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant myopathy characterized by slowly progressive skeletal muscle weakness and wasting. While a regenerative response is often provoked in many muscular dystrophies, little is known about whether a regenerative response is regularly elicited in FSHD muscle, prompting this study. For comparison, we also examined the similarly slowly progressing myotonic dystrophy type 2 (DM2). To first investigate regeneration at the transcriptomic level, we used the 200 human gene Hallmark Myogenesis list. This myogenesis biomarker was elevated in FSHD and control healthy myotubes compared to their myoblast counterparts, so is higher in myogenic differentiation. The myogenesis biomarker was also elevated in muscle biopsies from most independent FSHD, DM2 or Duchenne muscular dystrophy (DMD) studies compared to control biopsies, and on meta-analysis for each condition. In addition, the myogenesis biomarker was a robust binary discriminator of FSHD, DM2 and DMD from controls. We also analysed muscle regeneration at the protein level by immunolabelling muscle biopsies for developmental myosin heavy chain. Such immunolabelling revealed one or more regenerating myofibres in 76% of FSHD muscle biopsies from quadriceps and 91% from tibialis anterior. The mean proportion of regenerating myofibres per quadriceps biopsy was 0.48%, significantly less than 1.72% in the tibialis anterior. All DM2 muscle biopsies contained regenerating myofibres, with a mean of 1.24% per biopsy. Muscle regeneration in FSHD was correlated with the pathological hallmarks of fibre size variation, central nucleation, fibrosis and necrosis/regeneration/inflammation. In summary, the regenerative response in FSHD muscle biopsies correlates with the severity of pathology.

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