title: Corticosterone selectively targets endo-cortical surfaces by an osteoblast-dependent mechanism.
abstract: BACKGROUND
  The pathogenesis of glucocorticoid-induced osteoporosis remains ill defined. In this study, we examined the role of the osteoblast in mediating the effects of exogenous glucocorticoids on cortical and trabecular bone, employing the Col2.3-11βHSD2 transgenic mouse model of osteoblast-targeted disruption of glucocorticoid signalling.
  
  
  METHODS
  Eight week-old male transgenic (tg) and wild-type (WT) mice (n=20-23/group) were treated with either 1.5 mg corticosterone (CS) or placebo for 4 weeks. Serum tartrate-resistant acid phosphatase 5b (TRAP5b) and osteocalcin (OCN) were measured throughout the study. Tibiae and lumbar vertebrae were analysed by micro-CT and histomorphometry at endpoint.
  
  
  RESULTS
  CS suppressed serum OCN levels in WT and tg mice, although they remained higher in tg animals at all time points (p<0.05). Serum TRAP5b levels increased in WT mice only. The effect of CS on cortical bone differed by site: At the endosteal surface, exposure to CS significantly increased bone resorption and reduced bone formation, resulting in a larger bone marrow cavity cross-sectional area (p<0.01). In contrast, at the pericortical surface bone resorption was significantly decreased accompanied with a significant increase in pericortical cross-sectional area (p<0.05) while bone formation remained unaffected. Vertebral cortical thickness and area were reduced in CS treatment mice. Tg mice were partially protected from the effects of exogenous CS, both on a cellular and structural level. At the CS doses used in this study, trabecular bone remained largely unaffected.
  
  
  CONCLUSIONS
  Endocortical osteoblasts appear to be particularly sensitive to the detrimental actions of exogenous glucocorticoids. The increase in tibial pericortical cross-sectional area and the according changes in pericortical circumference suggest an anabolic bone response to GC treatment at this site. The protection of tg mice from these effects indicates that both catabolic and anabolic action of glucocorticoids are, at least in part, mediated by osteoblasts.
authors: Bone Research Program, ANZAC Research Institute, The University of Sydney, Sydney, Australia.
authors: Holger
authors: H
authors: Henneicke
authors: Markus
authors: M
authors: Herrmann
authors: Robert
authors: R
authors: Kalak
authors: Tara C
authors: TC
authors: Brennan-Speranza
authors: Uta
authors: U
authors: Heinevetter
authors: Nicky
authors: N
authors: Bertollo
authors: Robert E
authors: RE
authors: Day
authors: Dörte
authors: D
authors: Huscher
authors: Frank
authors: F
authors: Buttgereit
authors: Colin R
authors: CR
authors: Dunstan
authors: Markus J
authors: MJ
authors: Seibel
authors: Hong
authors: H
authors: Zhou
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D003345:Corticosterone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism*; D011859:Radiography; D013131:Spine / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000187:drug effects; D013499:Surface Properties / Q000187:drug effects; D013977:Tibia / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; D003345:Corticosterone