title: Mice lacking the intracellular cation channel TRIC-B have compromised collagen production and impaired bone mineralization.
abstract: The trimeric intracellular cation (TRIC) channels TRIC-A and TRIC-B localize predominantly to the endoplasmic reticulum (ER) and likely support Ca(2+) release from intracellular stores by mediating cationic flux to maintain electrical neutrality. Deletion and point mutations in TRIC-B occur in families with autosomal recessive osteogenesis imperfecta. Tric-b knockout mice develop neonatal respiratory failure and exhibit poor bone ossification. We investigated the cellular defect causing the bone phenotype. Bone histology indicated collagen matrix deposition was reduced in Tric-b knockout mice. Osteoblasts, the bone-depositing cells, from Tric-b knockout mice exhibited reduced Ca(2+) release from ER and increased ER Ca(2+) content, which was associated with ER swelling. These cells also had impaired collagen release without a decrease in collagen-encoding transcripts, consistent with a defect in trafficking of collagen through ER. In contrast, osteoclasts, the bone-degrading cells, from Tric-b knockout mice were similar to those from wild-type mice. Thus, TRIC-B function is essential to support the production and release of large amounts of collagen by osteoblasts, which is necessary for bone mineralization.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Chengzhu
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan. Keihanshin Consortium for Fostering the Next Generation of Global Leaders in Research (K-CONNEX), Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Ichimura
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Nianchao
authors.initials: N
authors.lastname: Qian
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Tsunaki
authors.initials: T
authors.lastname: Iida
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Daiju
authors.initials: D
authors.lastname: Yamazaki
authors.affiliation: Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Naruto
authors.initials: N
authors.lastname: Noma
authors.affiliation: Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Asagiri
authors.affiliation: Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Saitama Medical University, Saitama 350-0495, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Komazaki
authors.affiliation: National Institute of Advanced Industrial Science and Technology, Ibaraki 305-8568, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Sato
authors.affiliation: Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Aoyama
authors.affiliation: Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sawaguchi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Kakizawa
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nishi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan. takeshim@pharm.kyoto-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshima
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D002113:Calcification, Physiologic; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002412:Cations / Q000378:metabolism; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D005269:Femur / Q000378:metabolism; D006706:Homeostasis; D007473:Ion Channels / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D012886:Skull / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D002412:Cations; D007473:Ion Channels; C522222:TRIC-B protein, mouse; D003094:Collagen; D002118:Calcium