Nicole L. Jacobsen, Michael A. Nguyen, Aaron B. Morton, DDW Cornelison, Steven S. Segal
{"title":"Satellite Cell Ablation Limits Myofiber Regeneration but Not Angiogenesis Following Skeletal Muscle Injury","authors":"Nicole L. Jacobsen, Michael A. Nguyen, Aaron B. Morton, DDW Cornelison, Steven S. Segal","doi":"10.1111/micc.70024","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>Myotoxin injury of skeletal muscle disrupts myofibers and fragments capillaries. Following injury, myofibers and capillaries regenerate in concert; however, it remains unresolved whether myogenesis and angiogenesis are interdependent processes. We tested the hypothesis that myofiber regeneration is required for revascularization.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>To limit myofiber regeneration, satellite cells were depleted by tamoxifen injections (+TMX) in adult <i>Pax7-Cre</i><sup>ERT2<i>/+</i></sup>; <i>Rosa</i><sup>DTA<i>/+</i></sup> (Pax7-DTA) mice; vehicle injections (−TMX) served as controls. Two weeks later, the gluteus maximus muscle was injured by local injection of BaCl<sub>2</sub>. Regeneration of myofibers and microvessels was assessed histologically. Microvascular perfusion was evaluated with fluorescent tracers injected into the bloodstream.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Myofiber regeneration was minimal in +TMX. Through 21 days post injury (dpi), microvascular area (CD31 immunostaining) was similar between +TMX and −TMX, with disoriented microvessels prevailing in +TMX. At 7 dpi, fewer capillaries were perfused in +TMX compared to −TMX. At 21 dpi, EC area and capillary perfusion were not different between groups. For +TMX at 28 dpi, distinct regions with fewer perfused microvessels near “ghost” fibers were accompanied by adjacent areas of robust vascularity and clusters of adipocytes.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Following myotoxin injury after satellite cell ablation, angiogenesis ensues without myogenesis, and the microcirculation remodels according to changes in tissue composition.</p>\n </section>\n </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"32 7","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microcirculation","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/micc.70024","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective
Myotoxin injury of skeletal muscle disrupts myofibers and fragments capillaries. Following injury, myofibers and capillaries regenerate in concert; however, it remains unresolved whether myogenesis and angiogenesis are interdependent processes. We tested the hypothesis that myofiber regeneration is required for revascularization.
Methods
To limit myofiber regeneration, satellite cells were depleted by tamoxifen injections (+TMX) in adult Pax7-CreERT2/+; RosaDTA/+ (Pax7-DTA) mice; vehicle injections (−TMX) served as controls. Two weeks later, the gluteus maximus muscle was injured by local injection of BaCl2. Regeneration of myofibers and microvessels was assessed histologically. Microvascular perfusion was evaluated with fluorescent tracers injected into the bloodstream.
Results
Myofiber regeneration was minimal in +TMX. Through 21 days post injury (dpi), microvascular area (CD31 immunostaining) was similar between +TMX and −TMX, with disoriented microvessels prevailing in +TMX. At 7 dpi, fewer capillaries were perfused in +TMX compared to −TMX. At 21 dpi, EC area and capillary perfusion were not different between groups. For +TMX at 28 dpi, distinct regions with fewer perfused microvessels near “ghost” fibers were accompanied by adjacent areas of robust vascularity and clusters of adipocytes.
Conclusions
Following myotoxin injury after satellite cell ablation, angiogenesis ensues without myogenesis, and the microcirculation remodels according to changes in tissue composition.
期刊介绍:
The journal features original contributions that are the result of investigations contributing significant new information relating to the vascular and lymphatic microcirculation addressed at the intact animal, organ, cellular, or molecular level. Papers describe applications of the methods of physiology, biophysics, bioengineering, genetics, cell biology, biochemistry, and molecular biology to problems in microcirculation.
Microcirculation also publishes state-of-the-art reviews that address frontier areas or new advances in technology in the fields of microcirculatory disease and function. Specific areas of interest include: Angiogenesis, growth and remodeling; Transport and exchange of gasses and solutes; Rheology and biorheology; Endothelial cell biology and metabolism; Interactions between endothelium, smooth muscle, parenchymal cells, leukocytes and platelets; Regulation of vasomotor tone; and Microvascular structures, imaging and morphometry. Papers also describe innovations in experimental techniques and instrumentation for studying all aspects of microcirculatory structure and function.