HORMONAL REGULATION OF BONE COLLAGENASE MRNA

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The UMR 106-01 rat osteoblastic osteosarcoma cell line produces a neutral collagenase in response to parathyroid hormone (PTH) treatment. We have data demonstrating that the PTH control of collagenase gene expression in the UMR 106-01 cells is primarily at the transcriptional level. Using a partial rat collagenase clone which we isolated from a UMR 106-01 cDNA library, a 100-fold increase in the level of collagenase message 4 h after PTH treatment was observed along with a 4-6 fold increase in the rate of transcription. The time of induction correlates well with previous data demonstrating the stimulation of secretion of collagenase by PTH. Observations at the protein level also indicate that stimulation of collagenase production by PTH is mediated mainly by CAMP with a contributory effect of the calcium/protein kinase C message system. Thus, in order to study the regulation of collagenase gene expression, our goals are: 1) to delineate the mechanism of PTH stimulation of collagenase mRNA; 2) to clone the regulatory sequences associated with the rat collagenase gene; and 3) to identify DNA sequences important in transcriptional regulation of the UMR 106-01 collagenase gene. These data will contribute to the understanding of the regulation of collagenase gene expression and help to delineate the PTH regulatory pathway in an osteoblastic cell as well as aid in the normal and pathophysiological studies of bone resorption.