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.

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.

Skeletal muscle injury and repair: A role for complement

2018 ◽  
Vol 102 ◽  
pp. 165
Author(s):  
Erin Jacobs ◽  
Carolina Ortiz ◽  
Edouard Al-Chami ◽  
Mohsen Afshar ◽  
Clinton Robbins ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Injury ◽  
Skeletal Muscle Injury ◽  
Injury And Repair

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 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.

The Biological Use of Platelet-Rich Plasma in Skeletal Muscle Injury and Repair

2021 ◽  
pp. 036354652110616
Author(s):  
Jordan Boivin ◽  
Rachael Tolsma ◽  
Peter Awad ◽  
Keith Kenter ◽  
Yong Li
Keyword(s):  
Skeletal Muscle ◽  
Growth Factors ◽  
Regenerative Medicine ◽  
Sports Medicine ◽  
Muscle Injury ◽  
Blood Product ◽  
Platelet Rich Plasma ◽  
Injury And Repair ◽  
Current Report

Platelet-rich plasma (PRP) is a blood product that contains several growth factors and active proteins. PRP is thought to be used autologously to assist in the repair of injured tissues as well as to treat pain at the site of injury. The mechanism behind PRP in regenerative medicine has been well investigated and includes the identification and concentration of released growth factors and exosomes. The benefits of PRP have been highly recommended and are used widely in orthopaedics and sports medicine, including repair of injured skeletal muscle. This current report summarizes some of the more recent studies in the use of PRP as it relates to muscle healing, in both the in vitro and clinical arenas.

Inflammatory processes in muscle injury and repair

2005 ◽  
Vol 288 (2) ◽  
pp. R345-R353 ◽  
Author(s):  
James G. Tidball
Keyword(s):  
Skeletal Muscle ◽  
Growth Factors ◽  
Cell Invasion ◽  
Muscle Injury ◽  
Inflammatory Cell ◽  
Inflammatory Cells ◽  
Muscle Repair ◽  
Injury And Repair

Modified muscle use or injury can produce a stereotypic inflammatory response in which neutrophils rapidly invade, followed by macrophages. This inflammatory response coincides with muscle repair, regeneration, and growth, which involve activation and proliferation of satellite cells, followed by their terminal differentiation. Recent investigations have begun to explore the relationship between inflammatory cell functions and skeletal muscle injury and repair by using genetically modified animal models, antibody depletions of specific inflammatory cell populations, or expression profiling of inflamed muscle after injury. These studies have contributed to a complex picture in which inflammatory cells promote both injury and repair, through the combined actions of free radicals, growth factors, and chemokines. In this review, recent discoveries concerning the interactions between skeletal muscle and inflammatory cells are presented. New findings clearly show a role for neutrophils in promoting muscle damage soon after muscle injury or modified use. No direct evidence is yet available to show that neutrophils play a beneficial role in muscle repair or regeneration. Macrophages have also been shown capable of promoting muscle damage in vivo and in vitro through the release of free radicals, although other findings indicate that they may also play a role in muscle repair and regeneration through growth factors and cytokine-mediated signaling. However, this role for macrophages in muscle regeneration is still not definitive; other cells present in muscle can also produce the potentially regenerative factors, and it remains to be proven whether macrophage-derived factors are essential for muscle repair or regeneration in vivo. New evidence also shows that muscle cells can release positive and negative regulators of inflammatory cell invasion, and thereby play an active role in modulating the inflammatory process. In particular, muscle-derived nitric oxide can inhibit inflammatory cell invasion of healthy muscle and protect muscle from lysis by inflammatory cells in vivo and in vitro. On the other hand, muscle-derived cytokines can signal for inflammatory cell invasion, at least in vitro. The immediate challenge for advancing our current understanding of the relationships between muscle and inflammatory cells during muscle injury and repair is to place what has been learned in vitro into the complex and dynamic in vivo environment.

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