Mice lacking the intracellular cation channelTRIC-B have compromised collagen productionand impaired bone mineralization

摘要

The trimeric intracellular cation (TRIC) channels TRIC-A and TRIC-B localize predominantly to the endoplasmicreticulum (ER) and likely support Ca2+ release from intracellular stores by mediating cationic fluxto maintain electrical neutrality. Deletion and point mutations in TRIC-B occur in families with autosomalrecessive osteogenesis imperfecta. Tric-b knockout mice develop neonatal respiratory failure and exhibitpoor bone ossification. We investigated the cellular defect causing the bone phenotype. Bone histologyindicated collagen matrix deposition was reduced in Tric-b knockout mice. Osteoblasts, the bonedepositingcells, from Tric-b knockout mice exhibited reduced Ca2+ release from ER and increased ERCa2+ content, which was associated with ER swelling. These cells also had impaired collagen release withouta 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 fromwild-type mice. Thus, TRIC-B function is essential to support the production and release of large amountsof collagen by osteoblasts, which is necessary for bone mineralization.