Beck G R, Zerler B, Moran E
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8352-7. doi: 10.1073/pnas.140021997.
Osteopontin is a phosphorylated glycoprotein secreted to the mineralizing extracellular matrix by osteoblasts during bone development. It is believed to facilitate the attachment of osteoblasts and osteoclasts to the extracellular matrix, allowing them to perform their respective functions during osteogenesis. Several other functions have been suggested for this protein, and its up-regulation is associated with various disease states related to calcification, including arterial plaque formation and the formation of kidney stones. Although expression of this gene has been demonstrated in multiple tissues, its regulation is not well understood. Our previous studies on the roles of the retinoblastoma protein (pRB) and p300/CBP in the regulation of osteoblast differentiation revealed a link between osteopontin induction and the synthesis of alkaline phosphatase. In this paper, we describe results specifically linking induction of osteopontin to the enzymatic activity of alkaline phosphatase in the medium, which results in the generation of free phosphate. This elevation of free phosphate in the medium is sufficient to signal induction of osteopontin RNA and protein. The strong and specific induction of osteopontin in direct response to increased phosphate levels provides a mechanism to explain how expression of this product is normally regulated in bone and suggests how it may become up-regulated in damaged tissue.
骨桥蛋白是一种磷酸化糖蛋白，在骨骼发育过程中由成骨细胞分泌到矿化的细胞外基质中。据信它有助于成骨细胞和破骨细胞附着于细胞外基质，使它们在骨生成过程中发挥各自的功能。人们还提出了这种蛋白质的其他几种功能，其上调与多种与钙化相关的疾病状态有关，包括动脉斑块形成和肾结石形成。尽管该基因在多种组织中都有表达，但其调控机制尚不清楚。我们之前关于视网膜母细胞瘤蛋白（pRB）和p300/CBP在成骨细胞分化调控中作用的研究揭示了骨桥蛋白诱导与碱性磷酸酶合成之间的联系。在本文中，我们描述了具体将骨桥蛋白的诱导与培养基中碱性磷酸酶的酶活性联系起来的结果，这会导致游离磷酸盐的产生。培养基中游离磷酸盐的这种升高足以引发骨桥蛋白RNA和蛋白质的诱导。对磷酸盐水平升高直接产生的强烈而特异性的骨桥蛋白诱导提供了一种机制，来解释该产物在骨骼中正常调控的方式，并暗示了它在受损组织中可能上调的方式。
