REGULATION BY RETINOIC ACID OF OSTEOCLAST INTEGRINS

破骨细胞吸收骨的能力依赖于一个明确的 一系列的事件从他们与母体的连接开始。 这 结合在很大程度上由整合素α v β 3介导 从而调节异二聚体在细胞表面的表达 代表了控制再吸收过程的逻辑方法。 我们 发现视黄酸，类固醇激素超家族的一员， 其在体内和体外增强骨吸收，增加稳定的 说明β 3-整合素mRNA水平和α v β 3在 鸟类破骨细胞前体的表面。 我们假设： 第一章 视黄酸增强视黄酸介导的稳态β 3 mRNA水平 酸性受体介导的转录激活; （二） 维甲酸增强破骨细胞表面α v β 3表达 通过选择性合成为β 3亚基的前体;以及 第三章 视黄酸刺激的α v β 3表面表达， 前体增强破骨细胞附着于 基质并最终再吸收骨。 为了探索这些假设，我们建议： 第一章 表征响应于视黄酸的调节元件， β 3基因及其与视黄酸受体的相互作用。 （二） 确定视黄酸对合成和代谢的影响。 破骨细胞前体降解α v和β 3。 第三章 检查用维甲酸治疗破骨细胞前体的效果 酸对成熟破骨细胞附着于基质的能力的影响， 再吸收骨

The ability of osteoclasts to resorb bone relies on a well defined sequence of events starting with their attachment to matrix. This binding is mediated to a significant degree, by the integrin alphavbeta3 and thus, regulation of the heterodimer's expression on the cell surface represents a logical approach to controlling the resorptive process. We find that retinoic acid, a member of the steroid hormone superfamily which enhances bone resorption in vivo and in vitro, increases steady state levels of beta3-integrin mRNA and expression of alphavbeta3 on the surface of avian osteoclast precursors. We hypothesize that: 1) retinoic acid enhances steady state beta3 mRNA levels by retinoic acid receptor-mediated transcriptional activation; 2) retinoic acid enhances alphavbeta3 surface expression on osteoclast precursors by selective synthesis to the beta3 subunit; and 3) retinoic acid-stimulated alphavbeta3 surface expression by their precursors enhances the capacity of the osteoclasts to attach to matrix and ultimately resorb bone. To explore these hypotheses, we propose to: 1) Characterize the regulatory elements responding to retinoic acid in the beta3 gene and their interaction with retinoic acid receptor. 2) Determine the effects of retinoic acid on both synthesis and degradation of alphav and beta3 by osteoclast precursors. 3) Examine the effects of osteoclast precursor treatment with retinoic acid on the ability of mature osteoclasts to attach to matrix and resorb bone.