HORMONAL REGULATION OF BONE COLLAGENASE MRNA

UMR 106-01大鼠成骨肉瘤细胞系产生中性 胶原酶对甲状旁腺激素(PTH)治疗的反应。我们有 甲状旁腺素对胶原酶基因表达的调控作用 UMR 106-01细胞主要处于转录水平。使用 我们从UMR 106-01中分离的大鼠胶原酶部分克隆 图书馆，胶原酶消息水平在4小时后增加100倍 观察到甲状旁腺激素治疗的同时， 抄写。诱导的时间与之前的数据有很好的相关性 证明甲状旁腺激素对胶原酶的分泌有刺激作用。 蛋白质水平的观察也表明，刺激 甲状旁腺激素产生胶原酶主要由cAMP介导 钙/蛋白激酶C信息系统的贡献作用。因此， 为了研究胶原酶基因表达的调控，我们的目标是 1)阐明甲状旁腺素刺激胶原酶基因表达的机制； 2)克隆大鼠胶原酶相关调控序列 基因；以及3)鉴定在转录中重要的DNA序列 UMR 106-01胶原酶基因的调控。这些数据将有助于 对胶原酶基因表达调控的认识和对胶原酶基因表达的调控 有助于描述成骨细胞中的甲状旁腺素调节途径 以及对骨骼的正常和病理生理学研究的帮助 再吸收。

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.