title: Tusc2/Fus1 regulates osteoclast differentiation through NF-κB and NFATc1.
abstract: Tumor suppressor candidate 2 (Tusc2, also known as Fus1) regulates calcium signaling, and Ca2＋-dependent nuclear factor of activated T-cells (NFAT) and nuclear factor kappa B (NF-κB) pathways, which play roles in osteoclast differentiation. However, the role of Tusc2 in osteoclasts remains unknown. Here, we report that Tusc2 positively regulates the differentiation of osteoclasts. Overexpression of Tusc2 in osteoclast precursor cells enhanced receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation. In contrast, small interfering RNA-mediated knockdown of Tusc2 strongly inhibited osteoclast differentiation. In addition, Tusc2 induced the activation of RANKL-mediated NF-κB and calcium/calmodulin-dependent kinase IV (CaMKIV)/cAMP-response element (CRE)-binding protein CREB signaling cascades. Taken together, these results suggest that Tusc2 acts as a positive regulator of RANKL-mediated osteoclast differentiation. [BMB Reports 2017; 50(9): 454-459].
authors.affiliation: Departments of Pharmacology, Chonnam National University Medical School, Gwangju 61469, Korea.
authors.forename: Inyoung
authors.initials: I
authors.lastname: Kim
authors.affiliation: Departments of Pharmacology, Chonnam National University Medical School, Gwangju 61469, Korea.
authors.forename: Jung Ha
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Departments of Pharmacology, Chonnam National University Medical School, Gwangju 61469, Korea.
authors.forename: Kabsun
authors.initials: K
authors.lastname: Kim
authors.affiliation: Departments of Pharmacology and Biomedical Sciences, Chonnam National University Medical School, Gwangju 61469, Korea.
authors.forename: Semun
authors.initials: S
authors.lastname: Seong
authors.affiliation: Departments of Pharmacology and Biomedical Sciences, Chonnam National University Medical School, Gwangju 61469, Korea.
authors.forename: Nacksung
authors.initials: N
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D020013:Calcium Signaling / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D050778:NFATC Transcription Factors; D025521:Tumor Suppressor Proteins; C543627:Tusc2 protein, mouse