title: [Suppressive effects for osteoclastogenesis regulated by RANKL signal].
abstract: RANKL signal promotes osteoclast differentiation through a transcriptional activation of responsible genes for osteoclast formation and functions. Recent works revealed that RANKL signal plays a role to repress transcription of suppressive factors for osteoclastogenesis. Some transcriptional repressors actively inhibit expressions of osteoclast-specific genes in the precursors through canceling the functions of transcription activators to prevent uncontrollable osteoclast formation and pathological bone resorption. The mouse models lacking those transcriptional repressors exhibited accelerated osteoclast differentiation and bone loss. Although the suppressive factors are important for maintaining bone homeostasis, they have to be removed for osteoclast formation in the presence of RANKL. The transcriptional repressor Blimp1 was identified as a new target of RANKL signal and strongly attenuated expressions of various suppressive factors including Bcl6. The osteoclast-specific Blimp1 knockout mice exhibited defect of osteclast formation and loss of bone resorption. Thus, RANKL signal regulates osteoclast differentiation by inducing transcriptional activators such as NFATc1 as well as transcriptional repressors such as Blimp1.The former is essential for expressions of osteclast-specific genes, while the latter is required for terminating suppressions of osteoclast differentiation.
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, Japan.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Miyauchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyamoto
mesh_terms: D000818:Animals; D001862:Bone Resorption; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000502:physiology; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000502:physiology; D050835:Interferon Regulatory Factors / Q000502:physiology; D051379:Mice; D050778:NFATC Transcription Factors / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D051560:Proto-Oncogene Proteins c-bcl-6; D053245:RANK Ligand / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic; D000099185:Interferon Regulatory Factor-8
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D004268:DNA-Binding Proteins; D051798:Inhibitor of Differentiation Protein 1; D050835:Interferon Regulatory Factors; D050778:NFATC Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1; D051560:Proto-Oncogene Proteins c-bcl-6; D053245:RANK Ligand; D012097:Repressor Proteins; D000099185:Interferon Regulatory Factor-8; C084103:BCL6 protein, human; C497453:ID1 protein, human; C494003:NFATC1 protein, human; C087042:PRDM1 protein, human