title: ADP-Ribosylation Factor 1 Regulates Proliferation, Migration, and Fusion in Early Stage of Osteoclast Differentiation.
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.
authors.affiliation: Department of Microbiology, Laboratory of Bone Metabolism and Control, Yeungnam University College of Medicine, Daegu 705-717, Korea. t2phage@ynu.ac.kr.
authors.forename: Min Jae
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Laboratory of Bone Metabolism and Control, Yeungnam University College of Medicine, Daegu 705-717, Korea. hskim75@ynu.ac.kr.
authors.forename: Hyunsoo
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Oral Microbiology and Immunology, College of Dentistry, Wonkwang University, Iksan 570-749, Korea. leesh2@wku.ac.kr.|Center for Metabolic Function Regulation (CMFR), Wonkwang University School of Medicine, Iksan 570-749, Korea. leesh2@wku.ac.kr.
authors.forename: Seoung Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Center for Metabolic Function Regulation (CMFR), Wonkwang University School of Medicine, Iksan 570-749, Korea. mrwonsin@naver.com.
authors.forename: Dong Ryun
authors.initials: DR
authors.lastname: Gu
authors.affiliation: Department of Life Science and Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea. leesy@ewha.ac.kr.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Laboratory of Bone Metabolism and Control, Yeungnam University College of Medicine, Daegu 705-717, Korea. kyungheelee@ynu.ac.kr.
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Laboratory of Bone Metabolism and Control, Yeungnam University College of Medicine, Daegu 705-717, Korea. dwjeong@ynu.ac.kr.
authors.forename: Daewon
authors.initials: D
authors.lastname: Jeong
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D002459:Cell Fusion; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D008297:Male; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D020823:ADP-Ribosylation Factor 1
keywords: ADP-ribosylation factor 1; osteoclast differentiation; osteoclast fusion