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Mol Biol Rep. 2013 Mar;40(3):2097-105. doi: 10.1007/s11033-012-2268-6. Epub 2012 Dec 7.

Disruption of the transcription factor RBP-J results in osteopenia attributable to attenuated osteoclast differentiation.

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1
Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, China.

Abstract

The transcription factor recombination signal binding protein-Jκ (RBP-J) is the critical transcription factor downstream to all four mammalian Notch receptors. Although it has been reported that Notch signaling pathway is involved in bone remodeling, the importance of RBP-J in osteoclastogenesis has not been fully explored. To investigate the role of RBP-J in osteoclastogenesis, we conditionally deleted RBP-J systemically in bone marrow (BM) or specifically in macrophages. We found that disruption of RBP-J in BM resulted in an obvious decrease in trabecular bone mass associated with an increase in osteoclasts, leading to osteopenia. Disruption of RBP-J in macrophages phenocopied the phenotypes of RBP-J deletion in BM with respect to osteoclastogenesis, suggesting that the osteopenia in RBP-J deficient mice is essentially resulted from increased osteoclastogenesis. Furthermore, we found that RBP-J deletion in osteoclasts resulted in a dramatic increase in tartrate-resistant acid phosphatase expression. These findings demonstrate a negatively role of RBP-J in the differentiation of osteoclasts and suggest that Notch pathway may be a new therapeutic target for bone diseases related to increased osteoclastogenesis.

PMID:
23224519
DOI:
10.1007/s11033-012-2268-6
[Indexed for MEDLINE]
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