title: Disruption of the transcription factor RBP-J results in osteopenia attributable to attenuated osteoclast differentiation.
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.
authors.affiliation: Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Liu
authors.forename: Yi-Yang
authors.initials: YY
authors.lastname: Hu
authors.forename: Ya-Ning
authors.initials: YN
authors.lastname: Wei
authors.forename: Xing-Cheng
authors.initials: XC
authors.lastname: Zhao
authors.forename: Guang-Ying
authors.initials: GY
authors.lastname: Dong
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Qin
authors.forename: Yin
authors.initials: Y
authors.lastname: Ding
authors.forename: Hua
authors.initials: H
authors.lastname: Han
mesh_terms: D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics* / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D007527:Isoenzymes; C497571:Rbpj protein, mouse; D051880:Receptors, Notch; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase