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Type: Journal article
Title: Bril: A novel bone-specific modulator of mineralization
Author: Moffatt, P.
Gaumond, M.
Salois, P.
Sellin, K.
Bessette, M.
Godin, E.
De Oliveira, P.
Atkins, G.
Nanci, A.
Thomas, G.
Citation: Journal of Bone and Mineral Research, 2008; 23(9):1497-1508
Publisher: Amer Soc Bone & Mineral Res
Issue Date: 2008
ISSN: 0884-0431
Statement of
Pierre Moffatt, Marie-Helene Gaumond, Patrick Salois, Karine Sellin, Marie-Claude Bessette, Éric Godin, Paulo Tambasco de Oliveira, Gerald J Atkins, Antonio Nanci, Gethin Thomas
Abstract: In the course of attempting to define the bone "secretome" using a signal-trap screening approach, we identified a gene encoding a small membrane protein novel to osteoblasts. Although previously identified in silico as ifitm5, no localization or functional studies had been undertaken on this gene. We characterized the expression patterns and localization of this gene in vitro and in vivo and assessed its role in matrix mineralization in vitro. The bone specificity and shown role in mineralization led us to rename the gene bone restricted ifitm-like protein (Bril). Bril encodes a 14.8-kDa 134 amino acid protein with two transmembrane domains. Northern blot analysis showed bone-specific expression with no expression in other embryonic or adult tissues. In situ hybridization and immunohistochemistry in mouse embryos showed expression localized on the developing bone. Screening of cell lines showed Bril expression to be highest in osteoblasts, associated with the onset of matrix maturation/mineralization, suggesting a role in bone formation. Functional evidence of a role in mineralization was shown by adenovirus-mediated Bril overexpression and lentivirus-mediated Bril shRNA knockdown in vitro. Elevated Bril resulted in dose-dependent increases in mineralization in UMR106 and rat primary osteoblasts. Conversely, knockdown of Bril in MC3T3 osteoblasts resulted in reduced mineralization. Thus, we identified Bril as a novel osteoblast protein and showed a role in mineralization, possibly identifying a new regulatory pathway in bone formation.
Keywords: novel bone gene; osteoblast-specifi; mineralization; membrane protein; bone formation
RMID: 0020082430
DOI: 10.1359/JBMR.080412
Appears in Collections:Orthopaedics and Trauma publications

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