title: Identification of two-pore channel 2 as a novel regulator of osteoclastogenesis.
abstract: Osteoclast differentiation is one of the critical steps that control bone mass levels in osteoporosis, but the molecules involved in osteoclastogenesis are still incompletely understood. Here, we show that two-pore channel 2 (TPC2) is expressed in osteoclast precursor cells, and its knockdown (TPC2-KD) in these cells suppressed RANKL-induced key events including multinucleation, enhancement of tartrate-resistant acid phosphatase (TRAP) activities, and TRAP mRNA expression levels. With respect to intracellular signaling, TPC2-KD reduced the levels of the RANKL-induced dynamic waving of Ca(2+) in RAW cells. The search for the target of TPC2 identified that nuclear localization of NFATc1 is retarded in TPC2-KD cells. Finally, TPC2-KD suppressed osteoclastic pit formation in cultures. We conclude that TPC2 is a novel critical molecule for osteoclastogenesis.
authors: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Global Center of Excellence Program for Molecular Science for Tooth and Bone Diseases, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. Electronic address: tnotomi.gcoe@tmd.ac.jp.
authors: Takuya
authors: T
authors: Notomi
authors: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors: Yoichi
authors: Y
authors: Ezura
authors: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Global Center of Excellence Program for Molecular Science for Tooth and Bone Diseases, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. Electronic address: noda.mph@mri.tmd.ac.jp.
authors: Masaki
authors: M
authors: Noda
mesh_terms: D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D055785:Gene Knockdown Techniques; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism*; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D015220:Calcium Channels; D007527:Isoenzymes; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D002118:Calcium