损伤后肌肉的正常炎症和再生需要来自肌肉和非肌肉细胞的骨桥蛋白。

IF 5.3 2区 医学 Q2 CELL BIOLOGY
Dimuthu K Wasgewatte Wijesinghe, Eleanor J Mackie, Charles N Pagel
{"title":"损伤后肌肉的正常炎症和再生需要来自肌肉和非肌肉细胞的骨桥蛋白。","authors":"Dimuthu K Wasgewatte Wijesinghe,&nbsp;Eleanor J Mackie,&nbsp;Charles N Pagel","doi":"10.1186/s13395-019-0190-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Osteopontin is secreted by skeletal muscle myoblasts and macrophages, and its expression is upregulated in muscle following injury. Osteopontin is present in many different structural forms, which vary in their expression patterns and effects on cells. Using a whole muscle autograft model of muscle injury in mice, we have previously shown that inflammation and regeneration of muscle following injury are delayed by the absence of osteopontin. The current study was undertaken to determine whether muscle or non-muscle cells provide the source of osteopontin required for its role in muscle regeneration.</p><p><strong>Methods: </strong>The extensor digitorum longus muscle of wild-type and osteopontin-null mice was removed and returned to its bed in the same animal (autograft) or placed in the corresponding location in an animal of the opposite genotype (allograft). Grafts were harvested at various times after surgery and analysed by histology, flow cytometry and quantitative polymerase chain reaction. Data were analysed using one- or two-way ANOVA or Kruskal-Wallis test.</p><p><strong>Results: </strong>Immunohistochemistry confirmed that osteopontin was expressed by macrophages in osteopontin-null muscle allografts in wild-type hosts and by myoblasts in wild-type allografts in osteopontin-null hosts. The decrease in muscle fibre number observed in wild-type autografts following grafting and the subsequent appearance of regenerating fibres were delayed in both types of allografts to a similar extent as in osteopontin-null autografts. Infiltration of neutrophils, macrophages and M1 and M2 macrophage subtypes were also delayed by lack of osteopontin in the muscle and/or host. While the proportion of macrophages showing the M1 phenotype was not affected, the proportion showing the M2 phenotype was decreased by osteopontin deficiency. Expression of tumour necrosis factor-α and interleukin-4 was lower in osteopontin-null than in wild-type autografts, and there was no difference between the osteopontin-null graft types.</p><p><strong>Conclusions: </strong>Osteopontins from muscle and non-muscle sources are equally important in the acute response of muscle to injury, and cannot substitute for each other, suggesting that they play distinct roles in regulation of cell behaviour. Future studies of mechanisms of osteopontin's roles in acute muscle inflammation and regeneration will need to investigate responses to osteopontins derived from both myoblasts and macrophages.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":"9 1","pages":"6"},"PeriodicalIF":5.3000,"publicationDate":"2019-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13395-019-0190-5","citationCount":"20","resultStr":"{\"title\":\"Normal inflammation and regeneration of muscle following injury require osteopontin from both muscle and non-muscle cells.\",\"authors\":\"Dimuthu K Wasgewatte Wijesinghe,&nbsp;Eleanor J Mackie,&nbsp;Charles N Pagel\",\"doi\":\"10.1186/s13395-019-0190-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Osteopontin is secreted by skeletal muscle myoblasts and macrophages, and its expression is upregulated in muscle following injury. Osteopontin is present in many different structural forms, which vary in their expression patterns and effects on cells. Using a whole muscle autograft model of muscle injury in mice, we have previously shown that inflammation and regeneration of muscle following injury are delayed by the absence of osteopontin. The current study was undertaken to determine whether muscle or non-muscle cells provide the source of osteopontin required for its role in muscle regeneration.</p><p><strong>Methods: </strong>The extensor digitorum longus muscle of wild-type and osteopontin-null mice was removed and returned to its bed in the same animal (autograft) or placed in the corresponding location in an animal of the opposite genotype (allograft). Grafts were harvested at various times after surgery and analysed by histology, flow cytometry and quantitative polymerase chain reaction. Data were analysed using one- or two-way ANOVA or Kruskal-Wallis test.</p><p><strong>Results: </strong>Immunohistochemistry confirmed that osteopontin was expressed by macrophages in osteopontin-null muscle allografts in wild-type hosts and by myoblasts in wild-type allografts in osteopontin-null hosts. The decrease in muscle fibre number observed in wild-type autografts following grafting and the subsequent appearance of regenerating fibres were delayed in both types of allografts to a similar extent as in osteopontin-null autografts. Infiltration of neutrophils, macrophages and M1 and M2 macrophage subtypes were also delayed by lack of osteopontin in the muscle and/or host. While the proportion of macrophages showing the M1 phenotype was not affected, the proportion showing the M2 phenotype was decreased by osteopontin deficiency. Expression of tumour necrosis factor-α and interleukin-4 was lower in osteopontin-null than in wild-type autografts, and there was no difference between the osteopontin-null graft types.</p><p><strong>Conclusions: </strong>Osteopontins from muscle and non-muscle sources are equally important in the acute response of muscle to injury, and cannot substitute for each other, suggesting that they play distinct roles in regulation of cell behaviour. Future studies of mechanisms of osteopontin's roles in acute muscle inflammation and regeneration will need to investigate responses to osteopontins derived from both myoblasts and macrophages.</p>\",\"PeriodicalId\":21747,\"journal\":{\"name\":\"Skeletal Muscle\",\"volume\":\"9 1\",\"pages\":\"6\"},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2019-02-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1186/s13395-019-0190-5\",\"citationCount\":\"20\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Skeletal Muscle\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13395-019-0190-5\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Skeletal Muscle","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13395-019-0190-5","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 20

摘要

背景:骨桥蛋白由骨骼肌成肌细胞和巨噬细胞分泌,损伤后其在肌肉中的表达上调。骨桥蛋白以多种不同的结构形式存在,其表达模式和对细胞的影响各不相同。使用小鼠肌肉损伤的全肌肉自体移植模型,我们之前已经表明,骨桥蛋白的缺失延迟了损伤后肌肉的炎症和再生。目前的研究是为了确定肌肉细胞或非肌肉细胞是否提供骨桥蛋白的来源,以实现其在肌肉再生中的作用。方法:取野生型和骨桥蛋白缺失小鼠的指长伸肌,在同一动物(自体移植)内放回其床上,或置于相反基因型动物(同种异体移植)的相应位置。术后不同时间采集移植物,用组织学、流式细胞术和定量聚合酶链反应进行分析。数据分析采用单因素或双因素方差分析或Kruskal-Wallis检验。结果:免疫组化证实骨桥蛋白在无骨桥蛋白野生型宿主同种异体移植物中由巨噬细胞表达,在无骨桥蛋白野生型宿主同种异体移植物中由成肌细胞表达。在野生型自体移植物中观察到的移植后肌纤维数量的减少和随后再生纤维的出现在两种类型的同种异体移植物中都延迟了,其程度与骨桥蛋白缺失的自体移植物相似。中性粒细胞、巨噬细胞以及M1和M2亚型巨噬细胞的浸润也因肌肉和/或宿主中骨桥蛋白的缺乏而延迟。虽然显示M1表型的巨噬细胞比例不受影响,但显示M2表型的比例因骨桥蛋白缺乏而降低。肿瘤坏死因子-α和白细胞介素-4的表达在骨桥蛋白缺失的自体移植物中低于野生型,而在骨桥蛋白缺失的移植物类型之间无差异。结论:来自肌肉和非肌肉来源的骨桥蛋白在肌肉对损伤的急性反应中同样重要,并且不能相互替代,这表明它们在调节细胞行为方面发挥着不同的作用。骨桥蛋白在急性肌肉炎症和再生中的作用机制的未来研究将需要调查来自成肌细胞和巨噬细胞的骨桥蛋白的反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Normal inflammation and regeneration of muscle following injury require osteopontin from both muscle and non-muscle cells.

Normal inflammation and regeneration of muscle following injury require osteopontin from both muscle and non-muscle cells.

Normal inflammation and regeneration of muscle following injury require osteopontin from both muscle and non-muscle cells.

Normal inflammation and regeneration of muscle following injury require osteopontin from both muscle and non-muscle cells.

Background: Osteopontin is secreted by skeletal muscle myoblasts and macrophages, and its expression is upregulated in muscle following injury. Osteopontin is present in many different structural forms, which vary in their expression patterns and effects on cells. Using a whole muscle autograft model of muscle injury in mice, we have previously shown that inflammation and regeneration of muscle following injury are delayed by the absence of osteopontin. The current study was undertaken to determine whether muscle or non-muscle cells provide the source of osteopontin required for its role in muscle regeneration.

Methods: The extensor digitorum longus muscle of wild-type and osteopontin-null mice was removed and returned to its bed in the same animal (autograft) or placed in the corresponding location in an animal of the opposite genotype (allograft). Grafts were harvested at various times after surgery and analysed by histology, flow cytometry and quantitative polymerase chain reaction. Data were analysed using one- or two-way ANOVA or Kruskal-Wallis test.

Results: Immunohistochemistry confirmed that osteopontin was expressed by macrophages in osteopontin-null muscle allografts in wild-type hosts and by myoblasts in wild-type allografts in osteopontin-null hosts. The decrease in muscle fibre number observed in wild-type autografts following grafting and the subsequent appearance of regenerating fibres were delayed in both types of allografts to a similar extent as in osteopontin-null autografts. Infiltration of neutrophils, macrophages and M1 and M2 macrophage subtypes were also delayed by lack of osteopontin in the muscle and/or host. While the proportion of macrophages showing the M1 phenotype was not affected, the proportion showing the M2 phenotype was decreased by osteopontin deficiency. Expression of tumour necrosis factor-α and interleukin-4 was lower in osteopontin-null than in wild-type autografts, and there was no difference between the osteopontin-null graft types.

Conclusions: Osteopontins from muscle and non-muscle sources are equally important in the acute response of muscle to injury, and cannot substitute for each other, suggesting that they play distinct roles in regulation of cell behaviour. Future studies of mechanisms of osteopontin's roles in acute muscle inflammation and regeneration will need to investigate responses to osteopontins derived from both myoblasts and macrophages.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Skeletal Muscle
Skeletal Muscle CELL BIOLOGY-
CiteScore
9.10
自引率
0.00%
发文量
25
审稿时长
12 weeks
期刊介绍: The only open access journal in its field, Skeletal Muscle publishes novel, cutting-edge research and technological advancements that investigate the molecular mechanisms underlying the biology of skeletal muscle. Reflecting the breadth of research in this area, the journal welcomes manuscripts about the development, metabolism, the regulation of mass and function, aging, degeneration, dystrophy and regeneration of skeletal muscle, with an emphasis on understanding adult skeletal muscle, its maintenance, and its interactions with non-muscle cell types and regulatory modulators. Main areas of interest include: -differentiation of skeletal muscle- atrophy and hypertrophy of skeletal muscle- aging of skeletal muscle- regeneration and degeneration of skeletal muscle- biology of satellite and satellite-like cells- dystrophic degeneration of skeletal muscle- energy and glucose homeostasis in skeletal muscle- non-dystrophic genetic diseases of skeletal muscle, such as Spinal Muscular Atrophy and myopathies- maintenance of neuromuscular junctions- roles of ryanodine receptors and calcium signaling in skeletal muscle- roles of nuclear receptors in skeletal muscle- roles of GPCRs and GPCR signaling in skeletal muscle- other relevant aspects of skeletal muscle biology. In addition, articles on translational clinical studies that address molecular and cellular mechanisms of skeletal muscle will be published. Case reports are also encouraged for submission. Skeletal Muscle reflects the breadth of research on skeletal muscle and bridges gaps between diverse areas of science for example cardiac cell biology and neurobiology, which share common features with respect to cell differentiation, excitatory membranes, cell-cell communication, and maintenance. Suitable articles are model and mechanism-driven, and apply statistical principles where appropriate; purely descriptive studies are of lesser interest.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信