Vitro and in vivo models for screening compounds to prevent glucocorticoid-induced bone destruction
AssigneeBoard of Trustees of the University of Arkansas
InventorsStavros C. Manolagas, Robert L. Jilka, Robert S. Weinstein, Teresita Bellido
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Abstract
The present invention demonstrates that glucocorticoid-induced bone disease is due to changes in the birth and death rate of bone cells using a murine model of glucocorticoid excess as well as bone biopsy specimens obtained from patients with glucocorticoid-induced osteoporosis. This invention demonstrates that glucocorticoid administration increases apoptosis of mature osteoblasts and osteocytes and decreases bone formation rate and bone mineral density accompanied by defective osteoblastogenesis and osteoclastogenesis in the bone marrow.
Claims4
A method of screening for compounds that reduce the bone deteriorating effects of glucocorticoids, comprising the steps of:
- (a) contacting osteoblast and osteocyte cells in vitro with either a glucocorticoid alone or said glucocorticoid in combination with a test compound;
- and
- (b) comparing the number of osteoblast and osteocyte cells undergoing apoptosis following treatment with said glucocorticoid alone or following treatment with said glucocorticoid in combination with said test compound, wherein a lower number of apoptotic cells following treatment with said glucocorticoid in combination with said test compound than with said glucocorticoid alone indicates that the test compound reduces the bond deteriorating effects of said glucocorticoid.
A method of screening for glucocorticoid analogs that possess decreased apoptotic properties towards osteoblast and osteocyte cells, comprising the steps of:
- (a) contacting said cells in vitro with either a glucocorticoid or a glucocorticoid analog;
- and
- (b) comparing the number of apoptotic cells following treatment with said glucocorticoid or said glucocorticoid analog, wherein a lower number of apoptotic cells following treatment with said glucocorticoid analog than with said glucocorticoid is indicative of a glucocorticoid analog that possess decreased apoptotic properties towards said cells.
Dependencies are inferred from the claim text.