title: CCAAT/Enhancer-binding protein homologous protein (CHOP) decreases bone formation and causes osteopenia.
abstract: CCAAT enhancer-binding protein (C/EBP) homologous protein (CHOP), is a member of the C/EBP family of nuclear proteins and plays a role in osteoblastic and adipocytic cell differentiation. CHOP is necessary for normal bone formation, but the consequences of its overexpression in vivo are not known. To investigate the direct actions of CHOP on bone remodeling in vivo, we generated transgenic mice overexpressing CHOP under the control of the human osteocalcin promoter. CHOP transgenics exhibited normal weight and reduced bone mineral density. Static and dynamic femoral bone histomorphometry revealed that CHOP overexpression caused reduced trabecular bone volume, secondary to decreased bone formation rates. One of 2 lines displayed a decrease in the number of osteoblasts, but in vivo bromodeoxyuridine labeling demonstrated that CHOP overexpression did not have an effect on osteoblastic cell replication. The decreased osteoblast cell number was accounted by an increase in apoptosis, as determined by DNA fragmentation measured by transferase-mediated digoxigenin-deoxyuridine triphosphate (dUTP) in situ nick-end labeling (TUNEL) reaction. In conclusion, transgenic mice overexpressing CHOP in the bone microenvironment have impaired osteoblastic function leading to osteopenia.
authors.affiliation: Department of Research, Saint Francis Hospital and Medical Center, Hartford, CT, USA.
authors.forename: Renata C
authors.initials: RC
authors.lastname: Pereira
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Stadmeyer
authors.forename: Deanna L
authors.initials: DL
authors.lastname: Smith
authors.forename: Sheila
authors.initials: S
authors.lastname: Rydziel
authors.forename: Ernesto
authors.initials: E
authors.lastname: Canalis
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015152:Blotting, Northern; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000209:etiology* / Q000378:metabolism*; D016723:Bone Remodeling / Q000502:physiology*; D005269:Femur / Q000166:cytology / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics; D010012:Osteogenesis; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism*
chemical_list: D015675:Osteocalcin; D051742:Transcription Factor CHOP