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The localization of the functional glucocorticoid receptor alpha in human bone
1Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrookes Hospital, United Kingdom. eoa@liverpool.ac.uk
The Journal of Clinical Endocrinology and Metabolism
|February 26, 2000
Summary
Glucocorticoid receptor alpha (GRalpha) is present in human bone cells throughout life, from development to adulthood. This finding suggests direct mechanisms for glucocorticoid action on bone, excluding osteoclasts.
Area of Science:
- Skeletal Biology
- Endocrinology
- Cell Biology
Background:
- Glucocorticoids impact bone, but mechanisms remain unclear.
- Glucocorticoid receptors (GR) mediate cellular actions.
- GR presence in human bone in vivo is unreported.
Purpose of the Study:
- Investigate functional glucocorticoid receptor alpha (GRalpha) expression in developing and adult human bone in vivo.
- Determine the cellular localization of GRalpha in various human bone tissues.
Main Methods:
- Used affinity-purified polyclonal antibodies against GRalpha.
- Examined human bone sections: neonatal (rib, calvaria, vertebrae), adolescent (tibial growth plates), and adult (iliac crest biopsies).
Main Results:
- GRalpha detected in chondrocytes, osteoblasts, osteocytes, bone marrow mononuclear cells, and endothelial cells.
- GRalpha expression varied with developmental stage and bone type.
- GRalpha was notably absent in osteoclasts.
Conclusions:
- First demonstration of functional GRalpha in human bone in situ.
- Suggests direct glucocorticoid action on bone cells via GRalpha across lifespan.
- Absence in osteoclasts implies indirect mediation of glucocorticoid effects on bone resorption.