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Degenerative and regenerative features of myofibers differ among skeletal muscles in a murine model of muscular dystrophy

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Abstract

Skeletal muscle myofibers constantly undergo degeneration and regeneration. Histopathological features of 6 skeletal muscles (cranial tibial [CT], gastrocnemius, quadriceps femoris, triceps brachii [TB], lumbar longissimus muscles, and costal part of the diaphragm [CPD]) were compared using C57BL/10ScSn-Dmd mdx (mdx) mice, a model for muscular dystrophy versus control, C57BL/10 mice. Body weight and skeletal muscle mass were lower in mdx mice than the control at 4 weeks of age; these results were similar at 6–30 weeks. Additionally, muscular lesions were observed in all examined skeletal muscles in mdx mice after 4 weeks, but none were noted in the controls. Immunohistochemical staining revealed numerous paired box 7-positive satellite cells surrounding the embryonic myosin heavy chain-positive regenerating myofibers, while the number of the former and staining intensity of the latter decreased as myofiber regeneration progressed. Persistent muscular lesions were observed in skeletal muscles of mdx mice between 4 and 14 weeks of age, and normal myofibers decreased with age. Number of muscular lesions was lowest in CPD at all ages examined, while the ratio of normal myofibers was lowest in TB at 6 weeks. In CT, TB, and CPD, Iba1-positive macrophages, the main inflammatory cells in skeletal muscle lesions, showed a significant positive correlation with the appearance of regenerating myofibers. Additionally, B220-positive B-cells showed positive and negative correlation with regenerating and regenerated myofibers, respectively. Our data suggest that degenerative and regenerative features of myofibers differ among skeletal muscles and that inflammatory cells are strongly associated with regenerative features of myofibers in mdx mice.

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Abbreviations

CT:

Cranial tibial muscle

CPD:

Costal part of the diaphragm

GA:

Gastrocnemius muscle

HE:

Hematoxylin-eosin

LL:

Lumbar longissimus muscle

MRF:

Myogenic regulatory factor

MT:

Masson’s trichrome stain

QR:

Quadriceps femoris muscle

TB:

Triceps brachii muscle

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Acknowledgments

This study was supported by JSPS KAKENHI Grant Number 15J01551.

Authors’ contributions

YK conceptualized the study. TI, OI, TN, YE, and YK designed the experiments. TI performed the experiments and analyzed the data. TI, OI, and YK drafted the manuscript.

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Authors and Affiliations

  1. Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-Ku, Sapporo, 060-0818, Japan

    Teppei Ikeda, Osamu Ichii, Saori Otsuka-Kanazawa, Teppei Nakamura, Yaser Hosny Ali Elewa & Yasuhiro Kon

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  1. Teppei Ikeda
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  2. Osamu Ichii
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  3. Saori Otsuka-Kanazawa
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Correspondence to Yasuhiro Kon.

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Ikeda, T., Ichii, O., Otsuka-Kanazawa, S. et al. Degenerative and regenerative features of myofibers differ among skeletal muscles in a murine model of muscular dystrophy. J Muscle Res Cell Motil 37, 153–164 (2016). https://doi.org/10.1007/s10974-016-9452-6

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  • DOI: https://doi.org/10.1007/s10974-016-9452-6

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