title: Synchronized Cell Cycle Arrest Promotes Osteoclast Differentiation.
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 p27(Kip1). 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.
authors: Laboratory of Bone Metabolism and Control, Department of Microbiology, Yeungnam University College of Medicine, Daegu 42415, Korea. kms1@boditech.co.kr.
authors: Minsuk
authors: M
authors: Kwon
authors: Laboratory of Bone Metabolism and Control, Department of Microbiology, Yeungnam University College of Medicine, Daegu 42415, Korea. kjinman75@hotmail.com.
authors: Jin-Man
authors: JM
authors: Kim
authors: Laboratory of Bone Metabolism and Control, Department of Microbiology, Yeungnam University College of Medicine, Daegu 42415, Korea. kyungheelee@ynu.ac.kr.
authors: Kyunghee
authors: K
authors: Lee
authors: Department of Physiology, Yeungnam University College of Medicine, Daegu 42415, Korea. sypark@med.yu.ac.kr.
authors: So-Young
authors: SY
authors: Park
authors: Department of Public Health Administration, Hanyang Women's University, Seoul 04763, Korea. limhs@hywoman.ac.kr.
authors: Hyun-Sook
authors: HS
authors: Lim
authors: Clinical Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea. xotn91@kiom.re.kr.
authors: Taesoo
authors: T
authors: Kim
authors: Laboratory of Bone Metabolism and Control, Department of Microbiology, Yeungnam University College of Medicine, Daegu 42415, Korea. dwjeong@ynu.ac.kr.
authors: Daewon
authors: D
authors: Jeong
mesh_terms: D000818:Animals; D056657:Cathepsin K / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D015151:Immunoblotting; D039661:Integrin beta3 / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D051379:Mice; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism
chemical_list: D039661:Integrin beta3; D050778:NFATC Transcription Factors; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016173:Macrophage Colony-Stimulating Factor; D056657:Cathepsin K; C542312:Atp6v0d2 protein, mouse; D025262:Vacuolar Proton-Translocating ATPases
keywords: cell cycle arrest; cell synchronization; osteoclast differentiation