A mathematical model of skeletal muscle regeneration

Stephenson, Elizabeth; Kojouharov, Hristo V.

doi:10.1002/mma.4908

Cited by 11 publications

(7 citation statements)

References 22 publications

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“…Second, to prove that Cdk1 is deleted in satellite cells of Cdk1sc − mice at age 1.5 years, ideally, immunostaining should be used to prove that CDK1 expression is down-regulated in satellite cells. But it was technically difficult to verify CDK1 expression in the static state using immunohistochemistry because CDK1 is only expressed during cell division ( Ravnik and Wolgemuth, 1999 ) and skeletal muscle is a stable tissue that undergoes little turnover of nuclei ( Stephenson and Kojouharov, 2018 ). Accordingly, to confirm that Cdk1 was deleted in satellite cells even after 60 weeks of tamoxifen treatment, we performed genotyping instead of immunostaining.…”

Section: Discussionmentioning

confidence: 99%

“…Satellite cells, also known as muscle stem cells, play a significant role in myogenesis and muscle regeneration. Mammalian adult skeletal muscle is a relatively stable tissue that undergoes little cell death or nuclear fission during its normal life cycle ( Chargé and Rudnicki, 2004 ; Stephenson and Kojouharov, 2018 ). Accordingly, satellite cells are in a quiescent cell cycle state under normal conditions ( Relaix and Zammit, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

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Cyclin-Dependent Kinase 1 Is Essential for Muscle Regeneration and Overload Muscle Fiber Hypertrophy

Kobayashi

Tanaka

Mulati

et al. 2020

Front. Cell Dev. Biol.

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Satellite cell proliferation is an essential step in proper skeletal muscle development and muscle regeneration. However, the mechanisms regulating satellite cell proliferation are relatively unknown compared to the knowledge associated with the differentiation of satellite cells. Moreover, it is still unclear whether overload muscle fiber hypertrophy is dependent on satellite cell proliferation. In general, cell proliferation is regulated by the activity of cell cycle regulators, such as cyclins and cyclin-dependent kinases (CDKs). Despite recent reports on the function of CDKs and CDK inhibitors in satellite cells, the physiological role of Cdk1 in satellite cell proliferation remains unknown. Herein, we demonstrate that Cdk1 regulates satellite cell proliferation, muscle regeneration, and muscle fiber hypertrophy. Cdk1 is highly expressed in myoblasts and is downregulated upon myoblast differentiation. Inhibition of CDK1 activity inhibits myoblast proliferation. Deletion of Cdk1 in satellite cells leads to inhibition of muscle recovery after muscle injury due to reduced satellite cell proliferation in vivo . Finally, we provide direct evidence that Cdk1 expression in satellite cells is essential for overload muscle fiber hypertrophy in vivo . Collectively, our results demonstrate that Cdk1 is essential for myoblast proliferation, muscle regeneration, and muscle fiber hypertrophy. These findings could help to develop treatments for refractory muscle injuries and muscle atrophy, such as sarcopenia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cyclin-Dependent Kinase 1 Is Essential for Muscle Regeneration and Overload Muscle Fiber Hypertrophy

Kobayashi

Tanaka

Mulati

et al. 2020

Front. Cell Dev. Biol.

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show abstract

Section: Introductionmentioning

confidence: 99%

“…Mathematical models of muscle degradation and regeneration have been proposed to study muscular dystrophies [ 55 ]. In [ 56 ], a new mathematical model was presented to explore the healing process of healthy skeletal muscle. In cancer cachexia, the modeling work is limited and focuses on metabolic alterations and energy expenditures [ 57 , 58 ].…”

Section: Introductionmentioning

confidence: 99%

Mathematical Model of Muscle Wasting in Cancer Cachexia

Farhang‐Sardroodi

Wilkie

2020

JCM

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Cancer cachexia is a debilitating condition characterized by an extreme loss of skeletal muscle mass, which negatively impacts patients’ quality of life, reduces their ability to sustain anti-cancer therapies, and increases the risk of mortality. Recent discoveries have identified the myostatin/activin A/ActRIIB pathway as critical to muscle wasting by inducing satellite cell quiescence and increasing muscle-specific ubiquitin ligases responsible for atrophy. Remarkably, pharmacological blockade of the ActRIIB pathway has been shown to reverse muscle wasting and prolong the survival time of tumor-bearing animals. To explore the implications of this signaling pathway and potential therapeutic targets in cachexia, we construct a novel mathematical model of muscle tissue subjected to tumor-derived cachectic factors. The model formulation tracks the intercellular interactions between cancer cell, satellite cell, and muscle cell populations. The model is parameterized by fitting to colon-26 mouse model data, and the analysis provides insight into tissue growth in healthy, cancerous, and post-cachexia treatment conditions. Model predictions suggest that cachexia fundamentally alters muscle tissue health, as measured by the stem cell ratio, and this is only partially recovered by anti-cachexia treatment. Our mathematical findings suggest that after blocking the myostatin/activin A pathway, partial recovery of cancer-induced muscle loss requires the activation and proliferation of the satellite cell compartment with a functional differentiation program.

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“…Computational neuroscience-modeling techniques (using systems of ordinary differential equations) have been utilized to develop a reliable predictive outcome model for HPA-related issues, such as ultradian and circadian patterns in normal, depressed, post-traumatic stress disorder states, and their comorbid pain [1, 47, 49, 59]. In Prince et al [40], the authors modeled acute pain from a gating mechanism point of view, which assumes the flow of inputs through the spinal cord to the brain as a major contributor for the pain experience, and constructed a biologically plausible mathematical model.…”

Section: Introductionmentioning

confidence: 99%

Transitioning from acute to chronic pain: a simulation study of trajectories of low back pain

Bevers

et al. 2019

J Transl Med

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Background Identifying how pain transitions from acute to chronic is critical in designing effective prevention and management techniques for patients’ well-being, physically, psychosocially, and financially. There is an increasingly pressing need for a quantitative and predictive method to evaluate how low back pain trajectories are classified and, subsequently, how we can more effectively intervene during these progression stages. Methods In order to better understand pain mechanisms, we investigated, using computational modeling, how best to describe pain trajectories by developing a platform by which we studied the transition of acute chronic pain. Results The present study uses a computational neuroscience-based method to conduct such trajectory research, motivated by the use of hypothalamic–pituitary–adrenal (HPA) axis activity-history over a time-period as a way to mimic pain trajectories. A numerical simulation study is presented as a “ proof of concept ” for this modeling approach. Conclusions This model and its simulation results have highlighted the feasibility and the potential of developing such a broader model for patient evaluations.

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A mathematical model of skeletal muscle regeneration

Cited by 11 publications

References 22 publications

Cyclin-Dependent Kinase 1 Is Essential for Muscle Regeneration and Overload Muscle Fiber Hypertrophy

Cyclin-Dependent Kinase 1 Is Essential for Muscle Regeneration and Overload Muscle Fiber Hypertrophy

Mathematical Model of Muscle Wasting in Cancer Cachexia

Transitioning from acute to chronic pain: a simulation study of trajectories of low back pain

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