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

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 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.

Fusion and beyond: Satellite cell contributions to loading‐induced skeletal muscle adaptation

“…In recent years, alternative models for preventing satellite cell fusion in vivo have emerged. These models disrupt some aspect of satellite cell function via genetic means, 60 , 88 , 184 , 185 , 186 , 187 and have generally concluded that satellite cell‐mediated myonuclear accretion is required for overload‐induced hypertrophy. Given dissonance between results from the Pax7‐DTA mouse versus other models, we speculate that the presence of dysfunctional satellite cells could be more deleterious to load‐induced muscle adaptation than removing satellite cells from the muscle environment altogether; however, the muscle being overloaded (e.g., extensor digitorum longus versus plantaris), post‐surgery/stimulus recovery status, genetic background of the mice, diet, or a variety of other factors may also in part explain the discrepancy.…”

Overexpression of cholinergic receptor nicotinic gamma subunit inhibits proliferation and differentiation of bovine preadipocytes

“…Cell proliferation is regulated by cell cycle regulators [ 20 ]. Activation and aggregation of CDK and mitogen-dependent signaling pathways regulate adipocyte proliferation and maturation [ 21 ].…”

Tenogenic induction of human adipose-derived stem cells by soluble tendon extracellular matrix: composition and transcriptomic analyses

“…A list of proliferation genes was selected, such as marker of proliferation Ki-67 (MKI67), PCNA and MCM, which are established cell proliferation markers [34]. Additionally, another set of genes directly associated with cell proliferation, mitotic process and cell division [e.g., myeloblastosis proto-oncogene like 2 (MYBL2), budding uninhibited by benzimidazoles 1 (BUB1), polo-like kinase 1 (PLK1), cyclin-dependent kinase 1 (CDK1) and kinesin family member 11 (KIF11)] were also included [34][35][36]]. Based on our data, more abundant proliferation genes were upregulated in the tECM compared to Col1 groups, such as MKI67, MYBL2, BUB1, PLK1, CDK1 and KIF11 (Fig.…”