title: Constitutive activation of Gli2 impairs bone formation in postnatal growing mice.
abstract: Indian hedgehog (Ihh) signaling is indispensable for osteoblast differentiation during endochondral bone development in the mouse embryo. We have previously shown that the Gli2 transcription activator critically mediates Ihh function in osteoblastogenesis. To explore the possibility that activation of Hedgehog (Hh) signaling may enhance bone formation, we generated mice that expressed a constitutively active form of Gli2 in the Osx-lineage cells. Unexpectedly, these mice exhibited severe osteopenia due to a marked decrease in osteoblast number and function, although bone resorption was not affected. Quantitative analyses of the molecular markers indicated that osteoblast differentiation was impaired in the mutant mouse. However, the osteoblast-lineage cells isolated from these mice exhibited more robust osteoblast differentiation than normal in vitro. Similarly, pharmacological stimulation of Hh signaling enhanced osteoblast differentiation from Osx-expressing cells isolated from the wild-type mouse. Thus, even though Hh signaling directly promotes osteoblast differentiation in vitro, constitutive activation of this pathway impairs bone formation in vivo, perhaps through an indirect mechanism.
authors: Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
authors: Kyu Sang
authors: KS
authors: Joeng
authors: Fanxin
authors: F
authors: Long
mesh_terms: D000818:Animals; D001851:Bone Diseases, Metabolic / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D002454:Cell Differentiation; D005260:Female; D048788:Growth and Development; D053823:Hedgehog Proteins / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis; D015398:Signal Transduction; D000075746:Zinc Finger Protein Gli2
chemical_list: C000618551:Gli2 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D000075746:Zinc Finger Protein Gli2
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