The transcriptional cofactor Lbh regulates angiogenesis and endochondral bone formation during fetal bone development.
Lbh is thought to act as a transcriptional cofactor and is highly conserved among species. Here we show that Lbh is expressed in chondrocytes, cells of the perichondrium, and the primary spongiosa in fetal growth plates of mice and chickens. Lbh overexpression in chick wings, using the RCAS-retroviral vector strategy, results in shortened skeletal elements and delayed hypertrophic chondrocyte maturation and bone formation. Additionally, osteoclast and endothelial cell invasion are delayed in the Lbh-overexpressing bones. Finally, we find a dramatic suppression of Runx2 and VEGF mRNAs in chondrocytes and osteoblasts that overexpress Lbh. Strikingly, this abnormal bone development in infected limbs can be rescued by concurrent overexpression of Runx2. These results suggest that during endochondral bone formation, Lbh may negatively regulate vascular invasion and formation of the early ossification center at least in part by interfering with Runx2 and/or VEGF expression.
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Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Nishimori
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Provot
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Kronenberg
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D016475:3T3 Cells; D000818:Animals; D001846:Bone Development; D001842:Bone and Bones / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002642:Chick Embryo; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology; D017403:In Situ Hybridization; D051379:Mice; D008954:Models, Biological; D009389:Neovascularization, Pathologic; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010010:Osteoclasts / Q000378:metabolism; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D018797:Cell Cycle Proteins; D050659:Core Binding Factor Alpha 1 Subunit; C428223:Lbh protein, mouse; D009687:Nuclear Proteins; C493716:Runx2 protein, mouse; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A