Osteoblast-targeted disruption of glucocorticoid signalling does not delay intramembranous bone healing


Agnes J. Webera, Gang Lia, Robert Kalak, Janine Street, Frank Buttgereit, Colin R. Dunstan, Markus J. Seibel, and Hong Zhou


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. Experiments were performed using a well characterised mouse model in which intracellular glucocorticoid signalling was disrupted in osteoblasts through transgenic overexpression of 11β-hydroxysteroid-dehydrogenase type 2 (11β-HSD2) under the control of a collagen type I promoter (Col2.3-11β-HSD2). Unicortical bone defects (0.8 mm) 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. 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 Col2.3-11β-HSD2 transgenic animals and their wild-type littermates at all time-points. 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.