title: Conditional inactivation of noggin in the postnatal skeleton causes osteopenia.
abstract: Noggin is an antagonist of bone morphogenetic proteins (BMP), and its overexpression causes suppressed osteoblastogenesis and osteopenia. Global inactivation of Noggin results in severe developmental defects and prenatal lethality, but the consequences of the conditional inactivation of Noggin on the postnatal skeleton are not known. To study the function of noggin in osteoblasts, we generated tissue-specific null Noggin mice by mating Noggin conditional mice, where the Noggin allele is flanked by loxP sequences, with mice expressing the Cre recombinase under the control of the osteocalcin promoter (Oc-Cre). Noggin conditional null mice exhibited decreased weight, shortened femoral length, and generalized osteopenia. Bone histomorphometric and microarchitectural analyses of distal femurs revealed decreased bone volume due to a reduced number of trabeculae in 1- and 3-month-old Noggin conditional null mice. Vertebral microarchitecture confirmed the osteopenia observed in Noggin conditional null mice. Osteoclast number was increased in 1-month-old male Noggin conditional null mice, and bone formation was increased in 3-month-old mice, but female mice did not exhibit increased bone remodeling. In conclusion, Noggin inactivation causes osteopenia, suggesting that BMP in excess have a detrimental effect on bone or that noggin has a BMP-independent role in skeletal homeostasis.
authors.affiliation: Department of Research, Saint Francis Hospital and Medical Center, 114 Woodland Street, Hartford, CT 06105-1299, USA. ECanalis@stfranciscare.org
authors.forename: Ernesto
authors.initials: E
authors.lastname: Canalis
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Brunet
authors.forename: Kristen
authors.initials: K
authors.lastname: Parker
authors.forename: Stefano
authors.initials: S
authors.lastname: Zanotti
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001851:Bone Diseases, Metabolic / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000378:metabolism / Q000473:pathology; D006706:Homeostasis / Q000502:physiology; D019426:Integrases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015675:Osteocalcin / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000502:physiology; D000099176:Noggin Protein
chemical_list: D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D019426:Integrases; D015675:Osteocalcin; D000099176:Noggin Protein; C045073:Cre recombinase