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The Localization of the Functional Glucocorticoid Receptor in Human Bone

Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrookes Hospital (E.O.A., A.H., J.E.C.), Cambridge; Department of Clinical Chemistry, Royal Liverpool University Teaching Hospital (E.O.A.), Liverpool L7 8XP; and MRC Bone Research Group, Nuffield Orthopaedic Centre, University of Oxford, Redcliffe Hospital (V.K., J.T.T.), Oxford, United Kingdom

Address correspondence and requests for reprints to: Dr. Emmanuel Abu, Department of Clinical Chemistry, Royal Liverpool University Teaching Hospital, Duncan Building, Prescot Street, Liverpool L7 8XP, United Kingdom. E-mail: eoa{at}liverpool.ac.uk

Glucocorticoids have well-documented effects on the skeleton, although their mechanism of action is still poorly understood. The actions of glucocorticoids on bone cells are mediated, in part, directly via specific receptors. The presence of these receptors has been demonstrated in both rodent and human osteoblastic cells in vitro, but their presence in human bone in vivo has not been reported.

In this study, we have used specific affinity purified polyclonal antibodies to the functional glucocorticoid receptor (GR) to investigate its expression in both developing and adult human bone using sections of neonatal rib, calvarial, and vertebral bones, tibial growth plates from adolescents, and iliac crest biopsies from adults who were to undergo liver transplantation.

In the tibial growth plates, GR was predominantly expressed in the hypertrophic chondrocytes within the cartilage. In the primary spongiosa, the receptor was highly expressed by osteoblasts at sites of bone modeling. Within the bone marrow, receptors were also detected in mononuclear cells and in endothelial cells of blood vessels. In the neonatal rib and vertebrae, GR was widely distributed at sites of endochondral bone formation in resting, proliferating, mature, and hypertrophic chondrocytes. They were also highly expressed in osteoblasts at sites of bone modeling. At sites of intramembranous ossification in neonatal calvarial bone and rib periosteum, GR was widely expressed in cells within the fibrous tissue and in osteoblasts at both the bone-forming surface and at modeling sites. In the iliac crests from adults, GR was predominantly expressed in osteocytes. The receptors were not detected in osteoclasts.

Our results show for the first time the presence of the functional GR in human bone in situ and suggest that the actions of glucocorticoids on bone may be mediated, in part, directly via the GR at different stages of life. The absence of receptor expression in osteoclasts also suggests that the effects of glucocorticoids on bone resorption may be mediated indirectly.

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