title: Osteoblast-targeted disruption of glucocorticoid signalling does not delay intramembranous bone healing.
abstract: OBJECTIVE
  Glucocorticoids at pharmacological doses have been shown to interfere with fracture repair. The role of endogenous glucocorticoids in fracture healing is not well understood. We examined whether endogenous glucocorticoids affect bone healing in an in vivo model of cortical defect repair.
  
  
  METHODS
  Experiments were performed using a well characterised mouse model in which intracellular glucocorticoid signalling was disrupted in osteoblasts through transgenic overexpression of 11beta-hydroxysteroid-dehydrogenase type 2 (11beta-HSD2) under the control of a collagen type I promoter (Col2.3-11beta-HSD2). Unicortical bone defects (ø 0.8mm) were created in the tibiae of 7-week-old male transgenic mice and their wild-type littermates. Repair was assessed via histomorphometry, immunohistochemistry and microcomputed tomography (micro-CT) analysis at 1-3 weeks after defect creation.
  
  
  RESULTS
  At week 1, micro-CT images of the defect demonstrated formation of mineralized intramembranous bone which increased in volume and density by week 2. At week 3, healing of the defect was nearly complete in all animals. Analysis by histomorphometry and micro-CT revealed that repair of the bony defect was similar in Col2.3-11beta-HSD2 transgenic animals and their wild-type littermates at all time-points.
  
  
  CONCLUSIONS
  Disrupting endogenous glucocorticoid signalling in mature osteoblasts did not affect intramembranous fracture healing in a tibia defect repair model. It remains to be shown whether glucocorticoid signalling has a role in endochondral fracture healing.
authors.affiliation: Bone Research Program, ANZAC Research Institute, The University of Sydney, Hospital Road, Concord NSW 2139, Sydney, Australia.
authors.forename: Agnes J
authors.initials: AJ
authors.lastname: Weber
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Robert
authors.initials: R
authors.lastname: Kalak
authors.forename: Janine
authors.initials: J
authors.lastname: Street
authors.forename: Frank
authors.initials: F
authors.lastname: Buttgereit
authors.forename: Colin R
authors.initials: CR
authors.lastname: Dunstan
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Seibel
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002113:Calcification, Physiologic / Q000502:physiology*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D017102:Fracture Healing / Q000502:physiology*; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013977:Tibia / Q000000981:diagnostic imaging / Q000473:pathology / Q000502:physiology; D019076:Transgenes; D055114:X-Ray Microtomography
chemical_list: D024042:Collagen Type I; D005938:Glucocorticoids; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2