scholarly journals RNU (Foxn1RNU-Nude) Rats Demonstrate an Improved Ability to Regenerate Muscle in a Volumetric Muscle Injury Compared to Sprague Dawley Rats

2021 ◽  
Vol 8 (1) ◽  
pp. 12
Author(s):  
Michael J. McClure ◽  
Lucas C. Olson ◽  
David J. Cohen ◽  
Yen Chen Huang ◽  
Shirley Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Muscle Force ◽  
Immune Cell ◽  
Fiber Formation ◽  
Skeletal Muscle Regeneration ◽  
Host Responses ◽  
Sprague Dawley ◽  
Sd Rats ◽  
Fiber Number

Products developed for skeletal muscle regeneration frequently incorporate allogeneic and xenogeneic materials to elicit a regenerative response to heal skeletal muscle wounds. To avoid graft rejection in preclinical studies, immunodeficient rodents are used. Whether the immunodeficiency alters the host response to the material in skeletal muscle has not been studied. In this study, we hypothesized that an allogeneic acellular skeletal muscle grafts implanted in an immunodeficient rat (RNU, Foxn1-deficient) would exhibit better new muscle fiber formation compared to grafts implanted in immunocompetent Sprague Dawley (SD) rats. Decellularized SD skeletal muscle matrix (DMM) was implanted in the gastrocnemius (N = 8 rats/group). 56 days after surgery, animal gait was examined and animals were euthanized. Muscle force was assessed and fiber number as well as immune cell infiltrate was measured by histomorphometry and immunohistochemistry. Animal gait and percent recovery of muscle force were unchanged in both groups, but newly regenerated muscle fibers increased in RNU rats. Macrophage staining for CD68 was higher in RNU rats than in SD rats. These data show differences in muscle regeneration between animal models using the same biomaterial treatment, but these differences could not be ascribed to the immune response. Overall, our data provide awareness that more studies are needed to understand how host responses to biomaterials differ based on the animal model used.

scholarly journals Effects of intramuscular administration of 1α,25(OH)2D3 during skeletal muscle regeneration on regenerative capacity, muscular fibrosis, and angiogenesis

2016 ◽  
Vol 120 (12) ◽  
pp. 1381-1393 ◽  
Author(s):  
Ratchakrit Srikuea ◽  
Muthita Hirunsai
Keyword(s):  
Skeletal Muscle ◽  
Vitamin D ◽  
Protein Synthesis ◽  
Cell Differentiation ◽  
Satellite Cell ◽  
Muscle Regeneration ◽  
Fiber Type ◽  
Fiber Formation ◽  
Skeletal Muscle Regeneration ◽  
Type Composition

The recent discovery of the vitamin D receptor (VDR) in regenerating muscle raises the question regarding the action of vitamin D3 on skeletal muscle regeneration. To investigate the action of vitamin D3 on this process, the tibialis anterior muscle of male C57BL/6 mice (10 wk of age) was injected with 1.2% BaCl2 to induce extensive muscle injury. The bioactive form of vitamin D3 [1α,25(OH)2D3] was administered daily via intramuscular injections during the regenerative phase (days 4-7 postinjury). Physiological and supraphysiological doses of 1α,25(OH)2D3 relative to 1 μg/kg muscle wet weight and mouse body weight were investigated. Muscle samples were collected on day 8 postinjury to examine proteins related to vitamin D3 metabolism (VDR, CYP24A1, and CYP27B1), satellite cell differentiation and regenerative muscle fiber formation [myogenin and embryonic myosin heavy chain (EbMHC)], protein synthesis signaling (Akt, p70 S6K1, 4E-BP1, and myostatin), fiber-type composition (fast and slow MHCs), fibrous formation (vimentin), and angiogenesis (CD31). Administration of 1α,25(OH)2D3 at physiological and supraphysiological doses enhanced VDR expression in regenerative muscle. Moreover, CYP24A1 and vimentin expression was increased, accompanying decreased myogenin and EbMHC expression at the supraphysiological dose. However, there was no change in CYP27B1, Akt, p70 S6K1, 4E-BP1, myostatin, fast and slow MHCs, or CD31 expression at any dose investigated. Taken together, administration of 1α,25(OH)2D3 at a supraphysiological dose decreased satellite cell differentiation, delayed regenerative muscle fiber formation, and increased muscular fibrosis. However, protein synthesis signaling, fiber-type composition, and angiogenesis were not affected by either 1α,25(OH)2D3 administration at a physiological or supraphysiological dose.

scholarly journals Dynamic Expression and the Role of BDNF in Exercise-induced Skeletal Muscle Regeneration

2017 ◽  
Vol 38 (13) ◽  
pp. 959-966 ◽  
Author(s):  
Tao Yu ◽  
Yun Chang ◽  
Xiao Gao ◽  
Han Li ◽  
Peng Zhao
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Mrna Level ◽  
Elevated Serum ◽  
Skeletal Muscle Regeneration ◽  
Sprague Dawley ◽  
Bdnf Mrna ◽  
Post Exercise ◽  
Downhill Running ◽  
Exercise Induced

AbstractBrain-derived neurotrophic factor (BDNF) is a myokine. However, its role in skeletal muscle has not been well elucidated. In this study, we aimed to investigate its expression profile in skeletal muscle following downhill running and to explore its functions. Male Sprague Dawley rats were assigned to sedentary and downhill running groups. Tail vein blood, total mRNA and protein from soleus muscle was obtained from rats at different time points post-exercise (1d, 3d, 5d, 7d and 14d). We found a significant elevation of BDNF mRNA level 5d and 7d post-exercise (p<0.05), increased BDNF protein level 1d, 3d, 7d and 14d post-exercise (p<0.05), and continuously elevated serum BDNF level (p<0.05). In addition, serum creatine kinase activity was increased 5d following exercise (p<0.05); expression of MyoD was elevated (p<0.05); disruption of myofibers and centralized nuclei in damaged myofibers were clearly observed 1d and 5d post-exercise, respectively. Moreover, AMPK phosphorylation was present 1d post-exercise (p<0.05), while AKT was phosphorylated for 5d post-exercise (p<0.05). In conclusion, downhill running induces a time-dependent up-regulation of BDNF in skeletal muscle, which is involved in exercise-induced skeletal muscle regeneration.

Mitochondrial biogenesis during skeletal muscle regeneration

2002 ◽  
Vol 282 (4) ◽  
pp. E802-E809 ◽  
Author(s):  
Stéphanie Duguez ◽  
Léonard Féasson ◽  
Christian Denis ◽  
Damien Freyssenet
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Biogenesis ◽  
Transcriptional Activation ◽  
Muscle Regeneration ◽  
Citrate Synthase ◽  
Mrna Level ◽  
Skeletal Muscle Regeneration ◽  
Nuclear Antigen ◽  
Peroxisome Proliferator ◽  
Sprague Dawley

Myogenesis requires energy production for the execution of a number of regulatory and biosynthesis events. We hypothesized that mitochondrial biogenesis would be stimulated during skeletal muscle regeneration. Tibialis anterior muscles of male Sprague-Dawley rats were injected with 0.75% bupivacaine and removed at 3, 5, 7, 10, 14, 21, or 35 days after injection ( n = 5–7/group). Two main periods emerged from the histochemical analyses of muscle sections and the expression of proliferating cell nuclear antigen, desmin, and creatine phosphokinase: 1) activation/proliferation of satellite cells ( days 3–14) and 2) differentiation into muscle fibers ( days 5–35). The onset of muscle differentiation was accompanied by a marked stimulation of mitochondrial biogenesis, as indicated by a nearly fivefold increase in citrate synthase activity and state 3 rate of respiration between days 5 and 10. Peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) mRNA level and mitochondrial transcription factor A (mtTFA) protein level peaked on day 10 concurrently with the state 3 rate of respiration. Therefore, transcriptional activation by PGC-1 and mtTFA may be one of the mechanisms regulating mitochondrial biogenesis in regenerating skeletal muscle. Taken together, our results suggest that mitochondrial biogenesis may be an important regulatory event during muscle regeneration.

scholarly journals A cellular atlas of skeletal muscle regeneration and aging

2019 ◽  
Author(s):  
Bradley Pawlikowski ◽  
Nicole Dalla Betta ◽  
Tiffany Elston ◽  
Rebecca O’Rourke ◽  
Kenneth Jones ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Muscle Regeneration ◽  
Muscle Function ◽  
Immune Cell ◽  
Complex Structure ◽  
Skeletal Muscle Regeneration ◽  
Nerve Tissue ◽  
Post Injury ◽  
Muscle Stem Cell

SummaryAn individual skeletal muscle is a complex structure, composed of large contractile myofibers, connective tissue, nerve tissue, immune cells, stem cells and the vasculature. Each of these components contribute to skeletal muscle function, maintenance, regeneration, and if perturbed can potentially contribute to or cause disease that reduces muscle function. To investigate the cellular inventory of skeletal muscle we carried out single cell RNA sequencing on cells isolated from adult uninjured muscle, adult post injury muscle, and from aged uninjured muscle. Our muscle atlas provides the cellular landscape and partial transcriptome of pre-injury, post injury, and aged muscle, identifying dramatic changes in the muscle stem cell, fibroblast and immune cell populations during regeneration. Our data highlight dynamic changes occurring during muscle regeneration, identify potential extrinsic mechanisms that control muscle stem cell behavior, and underscore the inflamed state of aged uninjured muscle.

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