scholarly journals Tissue-Engineered Human Myobundle System as a Platform for Evaluation of Skeletal Muscle Injury Biomarkers

2020 ◽  
Vol 176 (1) ◽  
pp. 124-136
Author(s):  
Alastair Khodabukus ◽  
Amulya Kaza ◽  
Jason Wang ◽  
Neel Prabhu ◽  
Richard Goldstein ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Injury ◽  
Culture Media ◽  
Contractile Function ◽  
Significant Loss ◽  
Drug Induced ◽  
Skeletal Muscle Injury ◽  
Specificity And Sensitivity ◽  
Novel Biomarkers

Abstract Traditional serum biomarkers used to assess skeletal muscle damage, such as activity of creatine kinase (CK), lack tissue specificity and sensitivity, hindering early detection of drug-induced myopathies. Recently, a novel four-factor skeletal muscle injury panel (MIP) of biomarkers consisting of skeletal troponin I (sTnI), CK mass (CKm), fatty-acid-binding protein 3 (Fabp3), and myosin light chain 3, has been shown to have increased tissue specificity and sensitivity in rodent models of skeletal muscle injury. Here, we evaluated if a previously established model of tissue-engineered functional human skeletal muscle (myobundle) can allow detection of the MIP biomarkers after injury or drug-induced myotoxicity in vitro. We found that concentrations of three MIP biomarkers (sTnI, CKm, and Fabp3) in myobundle culture media significantly increased in response to injury by a known snake venom (notexin). Cerivastatin, a known myotoxic statin, but not pravastatin, induced significant loss of myobundle contractile function, myotube atrophy, and increased release of both traditional and novel biomarkers. In contrast, dexamethasone induced significant loss of myobundle contractile function and myotube atrophy, but decreased the release of both traditional and novel biomarkers. Dexamethasone also increased levels of matrix metalloproteinase-2 and -3 in the culture media which correlated with increased remodeling of myobundle extracellular matrix. In conclusion, this proof-of-concept study demonstrates that tissue-engineered human myobundles can provide an in vitro platform to probe patient-specific drug-induced myotoxicity and performance assessment of novel injury biomarkers to guide preclinical and clinical drug development studies.

Serum miR-206 as a biomarker for drug-induced skeletal muscle injury in rats

2020 ◽  
Vol 45 (8) ◽  
pp. 503-513
Author(s):  
Yu Yamaura ◽  
Masayuki Kanki ◽  
Daisuke Sasaki ◽  
Miki Nakajima ◽  
Akira Unami
Keyword(s):  
Skeletal Muscle ◽  
Muscle Injury ◽  
Drug Induced ◽  
Skeletal Muscle Injury

scholarly journals Response of Novel Skeletal Muscle Biomarkers in Dogs to Drug-Induced Skeletal Muscle Injury or Sustained Endurance Exercise.

2017 ◽  
pp. kfw262
Author(s):  
Katerina Vlasakova ◽  
Pamela Lane ◽  
Laura Michna ◽  
Nagaraja Muniappa ◽  
Frank D. Sistare ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endurance Exercise ◽  
Muscle Injury ◽  
Drug Induced ◽  
Skeletal Muscle Injury

scholarly journals Annexin A1 drives macrophage skewing towards a resolving phenotype to accelerate the regeneration of muscle injury through AMPK activation

2018 ◽  
Author(s):  
Simon McArthur ◽  
Thomas Gobbetti ◽  
Gaëtan Juban ◽  
Thibaut Desgeorges ◽  
Marine Theret ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Injury ◽  
Muscle Fibres ◽  
Annexin A1 ◽  
Skeletal Muscle Injury ◽  
Cellular Processes ◽  
Reparative Process ◽  
Injury And Repair ◽  
Inflammation Resolution

SummaryUnderstanding the circuits that promote an efficient resolution of inflammation is crucial to deciphering the molecular and cellular processes required to promote tissue repair. Macrophages play a central role in the regulation of inflammation, resolution and repair/regeneration. Using a model of skeletal muscle injury and repair, herein we identify Annexin A1 (AnxA1) as the extracellular trigger of macrophage skewing towards a pro-reparative phenotype. Brought into the injured tissue initially by migrated neutrophils, and then over-expressed in infiltrating macrophages, AnxA1 activates FPR2/ALX receptors and the downstream AMPK signalling cascade leading to macrophage skewing, dampening of inflammation and regeneration of muscle fibres. Mice lacking AnxA1 in all cells or in myeloid cells only display a defect in this reparative process.In vitroexperiments recapitulated these properties, with AMPK null macrophages lacking AnxA1-mediated polarization. Collectively, these data identify the AnxA1/FPR2/AMPK axis as a novel pathway in skeletal muscle injury regeneration.

Magnetic Targeting Improves the Therapeutic Efficacy of Microbubble-Mediated Obstructive Thrombus Sonothrombolysis

2019 ◽  
Vol 119 (11) ◽  
pp. 1752-1766 ◽  
Author(s):  
Xiaoqiang Chen ◽  
Weilan Wu ◽  
Shifei Wang ◽  
Jiayuan Zhong ◽  
Nima Moumin Djama ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Flow Velocity ◽  
Blood Flow Velocity ◽  
Muscle Injury ◽  
Magnetic Targeting ◽  
Skeletal Muscle Injury ◽  
The Us

Background Magnetic targeting may help microbubbles (MBs) reach obstructive thrombi and improve the efficacy of MB-mediated sonothrombolysis, but the role of magnetic targeting in MB-mediated sonothrombolysis remains elusive. Objectives We investigate the feasibility and efficacy of magnetically targeted MB-mediated sonothrombolysis for the treatment of obstructive thrombi. Materials and Methods Red and white thromboembolic models were established in vitro and in vivo. The models were randomly assigned to the control, ultrasound plus control MB (US + C-MB), ultrasound plus magnetic MB (US + M-MB), or US + M-MB + recombinant tissue-type plasminogen activator (r-tPA) groups and treated for 30 minutes. The recanalization rate, average blood flow velocity, hindlimb perfusion, and skeletal muscle injury marker levels were recorded. Results The recanalization rate, average blood flow velocity, and hindlimb perfusion in the red and white thromboembolic models were all significantly higher in the US + M-MB and US + M-MB + r-tPA groups than in the control and US + C-MB groups both in vitro and in vivo. Moreover, the levels of the skeletal muscle injury markers were all significantly lower in the US + M-MB and US + M-MB + r-tPA groups than in the other two groups in vivo for both thromboembolic models. However, the thrombolytic effects of red thrombi performed better than those of white thrombi in the US + M-MB + r-tPA group. Conclusion M-MB-mediated sonothrombolysis improves the efficacy of thrombolysis both in vitro and in vivo, and reduces tissue damage in clogging model; thus, this method may serve as a promising approach for treating thrombus-occlusive diseases.

scholarly journals The utility of monitoring skeletal muscle troponin I to detect drug‐ induced skeletal muscle injury

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Alan D Knapton ◽  
Parvaneh Espandiari ◽  
Azorides Morales ◽  
Mitra Moussazadeh ◽  
Terry Robins ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Injury ◽  
Troponin I ◽  
Drug Induced ◽  
Skeletal Muscle Injury

scholarly journals Evaluation of the Relative Performance of Drug-Induced Skeletal Muscle Injury Biomarkers in Rats

2015 ◽  
Vol 150 (1) ◽  
pp. 247-256 ◽  
Author(s):  
Peter M. Burch ◽  
David Greg Hall ◽  
Elizabeth G. Walker ◽  
William Bracken ◽  
Richard Giovanelli ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Injury ◽  
Relative Performance ◽  
Drug Induced ◽  
Skeletal Muscle Injury

scholarly journals Development of Microfluidic Stretch System for Studying Recovery of Damaged Skeletal Muscle Cells

Micromachines ◽  
2018 ◽  
Vol 9 (12) ◽  
pp. 671 ◽  
Author(s):  
Wanho Kim ◽  
Jaesang Kim ◽  
Hyung-Soon Park ◽  
Jessie Jeon
Keyword(s):  
Skeletal Muscle ◽  
Muscle Injury ◽  
Muscle Fibers ◽  
Movement Control ◽  
Muscle Cells ◽  
Cyclic Stretch ◽  
Intensity Change ◽  
Physical Damage ◽  
Skeletal Muscle Injury

The skeletal muscle occupies about 40% mass of the human body and plays a significant role in the skeletal movement control. Skeletal muscle injury also occurs often and causes pain, discomfort, and functional impairment in daily living. Clinically, most studies observed the recovery phenomenon of muscle by massage or electrical stimulation, but there are limitations on quantitatively analyzing the effects on recovery. Although additional efforts have been made within in vitro biochemical research, some questions still remain for effects of the different cell microenvironment for recovery. To overcome these limitations, we have developed a microfluidic system to investigate appropriate conditions for repairing skeletal muscle injury. First, the muscle cells were cultured in the microfluidic chip and differentiated to muscle fibers. After differentiation, we treated hydrogen peroxide and 18% axial stretch to cause chemical and physical damage to the muscle fibers. Then the damaged muscle fibers were placed under the cyclic stretch condition to allow recovery. Finally, we analyzed the damage and recovery by quantifying morphological change as well as the intensity change of intracellular fluorescent signals and showed the skeletal muscle fibers recovered better in the cyclic stretched condition. In total, our in situ generation of muscle damage and induction recovery platform may be a key system for investigating muscle recovery and rehabilitation.

Drug-induced mitochondrial dysfunction in cardiac and skeletal muscle injury

2008 ◽  
Vol 7 (2) ◽  
pp. 129-146 ◽  
Author(s):  
Vilma A Sardão ◽  
Sandro L Pereira ◽  
Paulo J Oliveira
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Muscle Injury ◽  
Drug Induced ◽  
Skeletal Muscle Injury

scholarly journals Analysis of a Skeletal Muscle Injury and Drug Interactions in Lovastatin- and Fenofibrate-Coadministered Dogs

2019 ◽  
Vol 38 (3) ◽  
pp. 192-201 ◽  
Author(s):  
Reo Kawata ◽  
Tsuyoshi Yokoi
Keyword(s):  
Skeletal Muscle ◽  
Drug Development ◽  
Plasma Levels ◽  
Muscle Injury ◽  
Adverse Reactions ◽  
Creatine Phosphokinase ◽  
Drug Induced ◽  
Skeletal Muscle Injury ◽  
Dog Model ◽  
Clinical Drug

Because dogs are widely used in drug development as nonrodent experimental animals, using a dog model for drug-induced adverse reactions is considered to be relevant for an evaluation and investigation of a mechanism and a biomarker of clinical drug-induced adverse reactions. Skeletal muscle injury occurs by various drugs, including statins and fibrates, during drug development. However, there is almost no report of a dog model for drug-induced skeletal muscle injury. In the present study, we induced skeletal muscle injury in dogs by oral coadministration of lovastatin (LV) and fenofibrate (FF) for 4 weeks. Increases in plasma levels of creatine phosphokinase, myoglobin, miR-1, and miR-133a and degeneration/necrosis of myofibers in skeletal muscles but not in the heart were observed in LV- and FF-coadministered dogs. Plasma levels of lovastatin lactone and lovastatin acid were higher in LV- and FF-coadministered dogs than LV-administered dogs. Taken together, FF coadministration is considered to affect LV metabolism and result in skeletal muscle injury.

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.

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