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Int. J. Mol. Sci. 2015, 16(12), 29305-29314; doi:10.3390/ijms161226168

ADP-Ribosylation Factor 1 Regulates Proliferation, Migration, and Fusion in Early Stage of Osteoclast Differentiation

1
Department of Microbiology, Laboratory of Bone Metabolism and Control, Yeungnam University College of Medicine, Daegu 705-717, Korea
2
Department of Oral Microbiology and Immunology, College of Dentistry, Wonkwang University, Iksan 570-749, Korea
3
Center for Metabolic Function Regulation (CMFR), Wonkwang University School of Medicine, Iksan 570-749, Korea
4
Department of Life Science and Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea
*
Authors to whom correspondence should be addressed.
Academic Editor: Alan C. Leonard
Received: 21 September 2015 / Revised: 2 December 2015 / Accepted: 3 December 2015 / Published: 9 December 2015
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
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Abstract

Small G-protein adenosine diphosphate (ADP)-ribosylation factors (ARFs) regulate a variety of cellular functions, including actin cytoskeleton remodeling, plasma membrane reorganization, and vesicular transport. Here, we propose the functional roles of ARF1 in multiple stages of osteoclast differentiation. ARF1 was upregulated during receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation and transiently activated in an initial stage of their differentiation. Differentiation of ARF1-deficient osteoclast precursors into mature osteoclasts temporarily increased in pre-maturation stage of osteoclasts followed by reduced formation of mature osteoclasts, indicating that ARF1 regulates the osteoclastogenic process. ARF1 deficiency resulted in reduced osteoclast precursor proliferation and migration as well as increasing cell-cell fusion. In addition, ARF1 silencing downregulated c-Jun N-terminal kinase (JNK), Akt, osteopontin, and macrophage colony-stimulating factor (M-CSF)-receptor c-Fms as well as upregulating several fusion-related genes including CD44, CD47, E-cadherin, and meltrin-α. Collectively, we showed that ARF1 stimulated proliferation and migration of osteoclast precursors while suppressing their fusion, suggesting that ARF1 may be a plausible inter-player that mediates the transition to osteoclast fusion at multiple steps during osteoclast differentiation View Full-Text
Keywords: ADP-ribosylation factor 1; osteoclast differentiation; osteoclast fusion ADP-ribosylation factor 1; osteoclast differentiation; osteoclast fusion
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Kim, M.J.; Kim, H.; Lee, S.H.; Gu, D.R.; Lee, S.Y.; Lee, K.; Jeong, D. ADP-Ribosylation Factor 1 Regulates Proliferation, Migration, and Fusion in Early Stage of Osteoclast Differentiation. Int. J. Mol. Sci. 2015, 16, 29305-29314.

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