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Int. J. Mol. Sci. 2016, 17(8), 1292; doi:10.3390/ijms17081292

Synchronized Cell Cycle Arrest Promotes Osteoclast Differentiation

1
Laboratory of Bone Metabolism and Control, Department of Microbiology, Yeungnam University College of Medicine, Daegu 42415, Korea
2
Department of Physiology, Yeungnam University College of Medicine, Daegu 42415, Korea
3
Department of Public Health Administration, Hanyang Women’s University, Seoul 04763, Korea
4
Clinical Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea
These authors contributed equally to this study.
*
Author to whom correspondence should be addressed.
Academic Editor: Ge Zhang
Received: 29 June 2016 / Revised: 2 August 2016 / Accepted: 4 August 2016 / Published: 9 August 2016
(This article belongs to the Special Issue Translational Molecular Medicine & Molecular Drug Discovery)
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Abstract

Osteoclast progenitors undergo cell cycle arrest before differentiation into osteoclasts, induced by exposure to macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). The role of such cell cycle arrest in osteoclast differentiation has remained unclear, however. We here examined the effect of synchronized cell cycle arrest on osteoclast formation. Osteoclast progenitors deprived of M-CSF in culture adopted a uniform morphology and exhibited cell cycle arrest at the G0–G1 phase in association with both down-regulation of cyclins A and D1 as well as up-regulation of the cyclin-dependent kinase inhibitor p27Kip1. Such M-CSF deprivation also promoted the differentiation of osteoclast progenitors into multinucleated osteoclasts expressing high levels of osteoclast marker proteins such as NFATc1, c-Fos, Atp6v0d2, cathepsin K, and integrin β3 on subsequent exposure to M-CSF and RANKL. Our results suggest that synchronized arrest and reprogramming of osteoclast progenitors renders them poised to respond to inducers of osteoclast formation. Further characterization of such effects may facilitate induction of the differentiation of heterogeneous and multipotent cells into desired cell lineages. View Full-Text
Keywords: cell cycle arrest; cell synchronization; osteoclast differentiation cell cycle arrest; cell synchronization; osteoclast differentiation
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MDPI and ACS Style

Kwon, M.; Kim, J.-M.; Lee, K.; Park, S.-Y.; Lim, H.-S.; Kim, T.; Jeong, D. Synchronized Cell Cycle Arrest Promotes Osteoclast Differentiation. Int. J. Mol. Sci. 2016, 17, 1292.

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