Cellular regulatory mechanisms that may underlie the effects of corticosteroids on bone.
The overall effects of corticosteroids on the skeleton are dependent on many factors including dose, duration of exposure to the steroid, steroid type and species. Some effects are indirect and are brought about by changes in, for example, parathyroid hormone secretion and intestinal calcium absorption, while others may result from cellular responses within the microenvironment of bone itself. Explants of trabecular bone are commonly used to study glucocorticoid effects in vitro, though it is often difficult to be certain that in vitro results directly reflect in vivo activity. Corticosteroids are dual inhibitors of cyclo-oxygenase and lipo-oxygenase, and may exert effects via inhibition of eicosanoid synthesis. They can also inhibit synthesis of cytokines, such as interleukin-1, which stimulate bone resorption and remodelling, by monocytes and macrophages. The production of cytokines and growth factors by bone cells themselves and the expression of their receptors may also be influenced by corticosteroids. Examples of corticosteroid-induced inhibition of synthesis include tumour necrosis factor and interleukin-6, and such effects may be important in explaining therapeutic actions of corticosteroids (e.g. in myeloma). Although it is not yet clear why different glucocorticoids have different effects, a number of factors determine the overall effect of a steroid. These include steroid metabolism and tissue distribution, selective effects on cytokine production, and tissue differences in gene transcription.
Department of Human Metabolism and Clinical Biochemistry, University Medical School, Sheffield.
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Russell
D001172:Arthritis, Rheumatoid / Q000378:metabolism; D001846:Bone Development / Q000187:drug effects*; D001857:Bone Matrix / Q000187:drug effects*; D046508:Culture Techniques; D016207:Cytokines / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans
D016207:Cytokines; D005938:Glucocorticoids