title: VapB as a regulator of osteoclastogenesis via modulation of PLCγ2-Ca(2+)-NFAT signaling.
abstract: VapB has been shown to regulate calcium homeostasis in amyotrophic lateral sclerosis. Calcium signaling is also important in metabolic bone diseases, but the role of VapB in the generation of osteoclasts for bone resorption during osteoclastogenesis is not known. Therefore, we investigated the role of VapB in RANKL-induced osteoclast differentiation. Interestingly, VapB is induced during osteoclastogenesis, and regulates osteoclast differentiation by modulating NFATc1. The results also suggest that VapB regulates osteoclastogenesis via PLCγ2-Ca(2+)-NFAT signaling. The involvement of PLCγ2-Ca(2+)-NFAT signaling in VapB-regulated osteoclastogenesis was confirmed by a pharmacological study. Taken together, the results indicate that VapB positively regulates RANKL-mediated osteoclastogenesis via PLCγ2-Ca(2+)-NFAT signaling.
authors.affiliation: Department of Anatomy and Institute for Skeletal Disease, Wonkwang University College of Medicine, 344-2 Sinyong-dong, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Sik-Won
authors.initials: SW
authors.lastname: Choi
authors.forename: Jeong-Tae
authors.initials: JT
authors.lastname: Yeon
authors.forename: Kie-In
authors.initials: KI
authors.lastname: Park
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Lee
authors.forename: Byung Soo
authors.initials: BS
authors.lastname: Youn
authors.forename: Jaemin
authors.initials: J
authors.lastname: Oh
authors.forename: Myeung Su
authors.initials: MS
authors.lastname: Lee
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism*; D053245:RANK Ligand / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D033921:Vesicular Transport Proteins
chemical_list: D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D053245:RANK Ligand; C529892:VAPB protein, mouse; D033921:Vesicular Transport Proteins; D051966:Phospholipase C gamma; D002118:Calcium