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Cyclin-dependent kinase 1 is essential for muscle regeneration and overload muscle fiber hypertrophy

Kobayashi, Yutaka ; Tanaka, Tomoyuki ; Mulati, Mieradilli ; Ochi, Hiroki ; Sato, Shingo ; Kaldis, Philipp LU orcid ; Yoshii, Toshitaka ; Okawa, Atsushi and Inose, Hiroyuki (2020) In Frontiers in Cell and Developmental Biology 8.
Abstract

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... (More)

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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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cdk1, cell cycle, frail, muscle injury, muscle regeneration, sarcopenia, satellite cell
in
Frontiers in Cell and Developmental Biology
volume
8
article number
564581
publisher
Frontiers Media S. A.
external identifiers
  • pmid:33163487
  • scopus:85094680821
ISSN
2296-634X
DOI
10.3389/fcell.2020.564581
language
English
LU publication?
yes
id
e1a0e9ac-42d5-4dfe-9933-411a3ad2fe57
date added to LUP
2020-11-09 09:12:42
date last changed
2024-06-14 02:06:24
@article{e1a0e9ac-42d5-4dfe-9933-411a3ad2fe57,
  abstract     = {{<p>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.</p>}},
  author       = {{Kobayashi, Yutaka and Tanaka, Tomoyuki and Mulati, Mieradilli and Ochi, Hiroki and Sato, Shingo and Kaldis, Philipp and Yoshii, Toshitaka and Okawa, Atsushi and Inose, Hiroyuki}},
  issn         = {{2296-634X}},
  keywords     = {{Cdk1; cell cycle; frail; muscle injury; muscle regeneration; sarcopenia; satellite cell}},
  language     = {{eng}},
  month        = {{10}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Cell and Developmental Biology}},
  title        = {{Cyclin-dependent kinase 1 is essential for muscle regeneration and overload muscle fiber hypertrophy}},
  url          = {{http://dx.doi.org/10.3389/fcell.2020.564581}},
  doi          = {{10.3389/fcell.2020.564581}},
  volume       = {{8}},
  year         = {{2020}},
}