scholarly journals NeuroHeal Improves Muscle Regeneration after Injury

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 22
Author(s):  
Sara Marmolejo-Martínez-Artesero ◽  
David Romeo-Guitart ◽  
Vanesa Venegas ◽  
Mario Marotta ◽  
Caty Casas
Keyword(s):  
Satellite Cell ◽  
Muscle Regeneration ◽  
Cell Biology ◽  
Fiber Type ◽  
Traumatic Injury ◽  
Injury Rate ◽  
Scar Tissue ◽  
Medical Problem ◽  
Preclinical Model

Musculoskeletal injuries represent a challenging medical problem. Although the skeletal muscle is able to regenerate and recover after injury, the process engaged with conservative therapy can be inefficient, leading to a high re-injury rate. In addition, the formation of scar tissue implies an alteration of mechanical properties in muscle. There is still a need for new treatments of the injured muscle. NeuroHeal may be one option. Published studies demonstrated that it reduces muscle atrophy due to denervation and disuse. The main objective of the present work was to assess the potential of NeuroHeal to improve muscle regeneration after traumatic injury. Secondary objectives included characterizing the effect of NeuroHeal treatment on satellite cell biology. We used a rat model of sport-induced injury in the gastrocnemius and analyzed the effects of NeuroHeal on functional recovery by means of electrophysiology and tetanic force analysis. These studies were accompanied by immunohistochemistry of the injured muscle to analyze fibrosis, satellite cell state, and fiber type. In addition, we used an in vitro model to determine the effect of NeuroHeal on myoblast biology and partially decipher its mechanism of action. The results showed that NeuroHeal treatment advanced muscle fiber recovery after injury in a preclinical model of muscle injury, and significantly reduced the formation of scar tissue. In vitro, we observed that NeuroHeal accelerated the formation of myotubes. The results pave the way for novel therapeutic avenues for muscle/tendinous disorders.

scholarly journals PEDF-derived peptide promotes skeletal muscle regeneration through its mitogenic effect on muscle progenitor cells

2015 ◽  
Vol 309 (3) ◽  
pp. C159-C168 ◽  
Author(s):  
Tsung-Chuan Ho ◽  
Yi-Pin Chiang ◽  
Chih-Kuang Chuang ◽  
Show-Li Chen ◽  
Jui-Wen Hsieh ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Proliferation ◽  
Cyclin D1 ◽  
Satellite Cell ◽  
Muscle Regeneration ◽  
Muscle Fibers ◽  
Skeletal Muscle Regeneration ◽  
Satellite Cell Proliferation

In response injury, intrinsic repair mechanisms are activated in skeletal muscle to replace the damaged muscle fibers with new muscle fibers. The regeneration process starts with the proliferation of satellite cells to give rise to myoblasts, which subsequently differentiate terminally into myofibers. Here, we investigated the promotion effect of pigment epithelial-derived factor (PEDF) on muscle regeneration. We report that PEDF and a synthetic PEDF-derived short peptide (PSP; residues Ser93-Leu112) induce satellite cell proliferation in vitro and promote muscle regeneration in vivo. Extensively, soleus muscle necrosis was induced in rats by bupivacaine, and an injectable alginate gel was used to release the PSP in the injured muscle. PSP delivery was found to stimulate satellite cell proliferation in damaged muscle and enhance the growth of regenerating myofibers, with complete regeneration of normal muscle mass by 2 wk. In cell culture, PEDF/PSP stimulated C2C12 myoblast proliferation, together with a rise in cyclin D1 expression. PEDF induced the phosphorylation of ERK1/2, Akt, and STAT3 in C2C12 myoblasts. Blocking the activity of ERK, Akt, or STAT3 with pharmacological inhibitors attenuated the effects of PEDF/PSP on the induction of C2C12 cell proliferation and cyclin D1 expression. Moreover, 5-bromo-2′-deoxyuridine pulse-labeling demonstrated that PEDF/PSP stimulated primary rat satellite cell proliferation in myofibers in vitro. In summary, we report for the first time that PSP is capable of promoting the regeneration of skeletal muscle. The signaling mechanism involves the ERK, AKT, and STAT3 pathways. These results show the potential utility of this PEDF peptide for muscle regeneration.

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.

The new target therapy to prevent weight gain associated to atypical antipsychotics: PKCβ

2017 ◽  
Vol 41 (S1) ◽  
pp. S370-S371
Author(s):  
C. Pavan ◽  
A. Rimessi ◽  
B. Zavan ◽  
V. Vindigni ◽  
P. Pinton
Keyword(s):  
Clinical Practice ◽  
Weight Gain ◽  
Side Effects ◽  
Cell Biology ◽  
Target Therapy ◽  
Premature Death ◽  
Preclinical Model ◽  
Psychomotor Tests

Antipsychotic drugs are currently used in clinical practice for a variety of mental disorders. Clozapine is the most effective medication for treatment-resistant schizophrenia, in controlling aggression and suicidal behavior in psychosis. Although clozapine is associated with a low likelihood of extrapyramidal symptoms and other neurological side effects, weight gain and metabolic side effects are well known in clinical practice exposing the patient to a greater risk of cardiovascular disorders, premature death, as well as psychosocial issues leading to non-adherence. The mechanisms underlying this pharmacologically activated disorders are still controversial. Based on our in vitro results, we have characterized in vivo the effects of the selective PKCβ inhibitor, Ruboxistaurin (LY-333531) on a preclinical model of long-term clozapine-induced weight gain. Cell biology, biochemistry and psychomotor tests have been performed on wild type and PKCβ (-/-) mutant mice to investigate the contribution of endogenous PKCβ and its pharmacological inhibitor on the neuroleptic effect of clozapine. Lastly, we also shed light on a novel aspect of the mechanism underlying of clozapine-induced weight gain, demonstrating that the clozapine-dependent PKCβ activation promote the inhibition of the lipid droplet-selective autophagy process, opening the way to new therapeutic intervention approach.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Acute molecular response of mouse hindlimb muscles to chronic stimulation

2009 ◽  
Vol 297 (3) ◽  
pp. C556-C570 ◽  
Author(s):  
W. A. LaFramboise ◽  
R. C. Jayaraman ◽  
K. L. Bombach ◽  
D. P. Ankrapp ◽  
J. M. Krill-Burger ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Satellite Cell ◽  
Fiber Type ◽  
Peroxisome Proliferator ◽  
Molecular Response ◽  
Activating Transcription Factor 3 ◽  
Glycogen Depletion ◽  
Activated T Cells

Stimulation of the mouse hindlimb via the sciatic nerve was performed for a 4-h period to investigate acute muscle gene activation in a model of muscle phenotype conversion. Initial force production (1.6 ± 0.1 g/g body wt) declined 45% within 10 min and was maintained for the remainder of the experiment. Force returned to initial levels upon study completion. An immediate-early growth response was present in the extensor digitorum longus (EDL) muscle (FOS, JUN, activating transcription factor 3, and musculoaponeurotic fibrosarcoma oncogene) with a similar but attenuated pattern in the soleus muscle. Transcript profiles showed decreased fast fiber-specific mRNA (myosin heavy chains 2A and 2B, fast troponins T3and I, α-tropomyosin, muscle creatine kinase, and parvalbumin) and increased slow transcripts (myosin heavy chain-1β/slow, troponin C slow, and tropomyosin 3y) in the EDL versus soleus muscles. Histological analysis of the EDL revealed glycogen depletion without inflammatory cell infiltration in stimulated versus control muscles, whereas ultrastructural analysis showed no evidence of myofiber damage after stimulation. Multiple fiber type-specific transcription factors (tea domain family member 1, nuclear factor of activated T cells 1, peroxisome proliferator-activated receptor-γ coactivator-1α and -β, circadian locomotor output cycles kaput, and hypoxia-inducible factor-1α) increased in the EDL along with transcription factors characteristic of embryogenesis (Kruppel-like factor 4; SRY box containing 17; transcription factor 15; PBX/knotted 1 homeobox 1; and embryonic lethal, abnormal vision). No established in vivo satellite cell markers or genes activated in our parallel experiments of satellite cell proliferation in vitro (cyclins A2, B2, C, and E1and MyoD) were differentially increased in the stimulated muscles. These results indicated that the molecular onset of fast to slow phenotype conversion occurred in the EDL within 4 h of stimulation without injury or satellite cell recruitment. This conversion was associated with the expression of phenotype-specific transcription factors from resident fiber myonuclei, including the activation of nascent developmental transcriptional programs.

Systemic administration of the NF-κB inhibitor curcumin stimulates muscle regeneration after traumatic injury

1999 ◽  
Vol 277 (2) ◽  
pp. C320-C329 ◽  
Author(s):  
Deepa Thaloor ◽  
Kristy J. Miller ◽  
Jonathan Gephart ◽  
Patrick O. Mitchell ◽  
Grace K. Pavlath
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Tissue Injury ◽  
Traumatic Injury ◽  
Systemic Administration ◽  
Muscle Injuries ◽  
Developmental Defects ◽  
Cell Proliferation And Differentiation

Skeletal muscle is often the site of tissue injury due to trauma, disease, developmental defects or surgery. Yet, to date, no effective treatment is available to stimulate the repair of skeletal muscle. We show that the kinetics and extent of muscle regeneration in vivo after trauma are greatly enhanced following systemic administration of curcumin, a pharmacological inhibitor of the transcription factor NF-κB. Biochemical and histological analyses indicate an effect of curcumin after only 4 days of daily intraperitoneal injection compared with controls that require >2 wk to restore normal tissue architecture. Curcumin can act directly on cultured muscle precursor cells to stimulate both cell proliferation and differentiation under appropriate conditions. Other pharmacological and genetic inhibitors of NF-κB also stimulate muscle differentiation in vitro. Inhibition of NF-κB-mediated transcription was confirmed using reporter gene assays. We conclude that NF-κB exerts a role in regulating myogenesis and that modulation of NF-κB activity within muscle tissue is beneficial for muscle repair. The striking effects of curcumin on myogenesis suggest therapeutic applications for treating muscle injuries.

scholarly journals Fusion-Independent Satellite Cell Communication to Muscle Fibers During Load-Induced Hypertrophy

Function ◽  
2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Kevin A Murach ◽  
Ivan J Vechetti ◽  
Douglas W Van Pelt ◽  
Samuel E Crow ◽  
Cory M Dungan ◽  
...  
Keyword(s):  
Satellite Cell ◽  
Cell Fusion ◽  
Satellite Cells ◽  
Cell Biology ◽  
Mechanical Load ◽  
Muscle Fibers ◽  
Cell Communication ◽  
Hypertrophic Growth

Abstract The “canonical” function of Pax7+ muscle stem cells (satellite cells) during hypertrophic growth of adult muscle fibers is myonuclear donation via fusion to support increased transcriptional output. In recent years, however, emerging evidence suggests that satellite cells play an important secretory role in promoting load-mediated growth. Utilizing genetically modified mouse models of delayed satellite cell fusion and in vivo extracellular vesicle (EV) tracking, we provide evidence for satellite cell communication to muscle fibers during hypertrophy. Myogenic progenitor cell-EV-mediated communication to myotubes in vitro influences extracellular matrix (ECM)-related gene expression, which is congruent with in vivo overload experiments involving satellite cell depletion, as well as in silico analyses. Satellite cell-derived EVs can transfer a Cre-induced, cytoplasmic-localized fluorescent reporter to muscle cells as well as microRNAs that regulate ECM genes such as matrix metalloproteinase 9 (Mmp9), which may facilitate growth. Delayed satellite cell fusion did not limit long-term load-induced muscle hypertrophy indicating that early fusion-independent communication from satellite cells to muscle fibers is an underappreciated aspect of satellite cell biology. We cannot exclude the possibility that satellite cell-mediated myonuclear accretion is necessary to maintain prolonged growth, specifically in the later phases of adaptation, but these data collectively highlight how EV delivery from satellite cells can directly contribute to mechanical load-induced muscle fiber hypertrophy, independent of cell fusion to the fiber.

Correlative microscopy in distrubuted (client/server) computing environments: tools for catalyzing the rapid dissemination of information about the cell biology of the human prostate

1995 ◽  
Vol 53 ◽  
pp. 682-683
Author(s):  
A. Hakam ◽  
J.T. Gau ◽  
M.L. Grove ◽  
B.A. Evans ◽  
M. Shuman ◽  
...  
Keyword(s):  
United States ◽  
Cell Biology ◽  
Tissue Bank ◽  
The United States ◽  
Prostate Adenocarcinoma ◽  
Correlative Microscopy ◽  
Client Server ◽  
Critical Elements ◽  
Transplant Organ

Prostate adenocarcinoma is the most common malignant tumor of men in the United States and is the third leading cause of death in men. Despite attempts at early detection, there will be 244,000 new cases and 44,000 deaths from the disease in the United States in 1995. Therapeutic progress against this disease is hindered by an incomplete understanding of prostate epithelial cell biology, the availability of human tissues for in vitro experimentation, slow dissemination of information between prostate cancer research teams and the increasing pressure to “ stretch” research dollars at the same time staff reductions are occurring.To meet these challenges, we have used the correlative microscopy (CM) and client/server (C/S) computing to increase productivity while decreasing costs. Critical elements of our program are as follows:1) Establishing the Western Pennsylvania Genitourinary (GU) Tissue Bank which includes >100 prostates from patients with prostate adenocarcinoma as well as >20 normal prostates from transplant organ donors.

Cytocompatibility and Material Properties of Poly-carbonate Urethane/Carbon Nanofiber Composites for Neural Applications

2003 ◽  
Vol 774 ◽  
Author(s):  
Janice L. McKenzie ◽  
Michael C. Waid ◽  
Riyi Shi ◽  
Thomas J. Webster
Keyword(s):  
Mechanical Properties ◽  
Carbon Nanofibers ◽  
Material Properties ◽  
Carbon Nanofiber ◽  
Scar Tissue ◽  
Tissue Response ◽  
Positive Interactions ◽  
Weight Percentage ◽  
Poly Carbonate

AbstractCarbon nanofibers possess excellent conductivity properties, which may be beneficial in the design of more effective neural prostheses, however, limited evidence on their cytocompatibility properties exists. The objective of the present in vitro study was to determine cytocompatibility and material properties of formulations containing carbon nanofibers to predict the gliotic scar tissue response. Poly-carbonate urethane was combined with carbon nanofibers in varying weight percentages to provide a supportive matrix with beneficial bulk electrical and mechanical properties. The substrates were tested for mechanical properties and conductivity. Astrocytes (glial scar tissue-forming cells) were seeded onto the substrates for adhesion. Results provided the first evidence that astrocytes preferentially adhered to the composite material that contained the lowest weight percentage of carbon nanofibers. Positive interactions with neurons, and, at the same time, limited astrocyte functions leading to decreased gliotic scar tissue formation are essential for increased neuronal implant efficacy.

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