OSTEOCLAST DIFFERENTIATION BY MESENCHYMAL CELLS

描述（由申请人提供）：破骨细胞分化增加， 导致慢性骨质疏松症的主要机制 损失因此，提高了对这些疾病发病机制的认识， 条件需要破骨细胞分化的详细知识。 破骨细胞的分化是通过与一层间充质细胞接触来刺激的。 支持细胞是成骨细胞谱系中相对不成熟的成员。 我们最近发现，与间充质细胞接触的效果 层反映了由间充质细胞产生的细胞外基质 和细胞表面分子。尽管其中一种分子RANKL具有 最近发现，其他细胞外基质/细胞表面的性质 参与这一过程的分子还不完全清楚。这 该项目将测试特定细胞表面和/或 除了RANKL外，细胞外基质分子由间充质细胞产生。 细胞以支持破骨细胞分化。为此，我们将利用 噬菌体展示文库以选择特异性结合所述抗体的肽。 支持破骨细胞分化的间充质细胞， 这些肽调节破骨细胞分化，并鉴定了 细胞外基质/细胞表面分子结合这些肽。这 该项目将提供有关细胞外的重要新信息 间充质细胞产生的基质/细胞表面分子，以支持 破骨细胞分化该项目还将确定新的肽， 特异性抑制破骨细胞分化，因此， 拟肽药物发现计划的有用起点， 慢性骨质流失的症状。

DESCRIPTION (provided by applicant): Increased osteoclast differentiation is the primary mechanism responsible for most conditions that cause chronic bone loss. Thus, improved understanding of the pathogenesis responsible for these conditions requires detailed knowledge of osteoclast differentiation. Osteoclast differentiation is stimulated by contact with a layer of mesenchymal support cells, which are relatively immature members of the osteoblast lineage. We have recently shown that the effect of contact with the mesenchymal cell layer reflects production by the mesenchymal cells of both extracellular matrix and cell surface molecules. Although one of these molecules, RANKL, has recently been identified, the nature of other extracellular matrix/cell surface molecules that are involved in this process is incompletely understood. This project will test the hypothesis that specific cell surface and/or extracellular matrix molecules in addition to RANKL are produced by mesenchymal cells to support osteoclast differentiation. For this purpose, we will utilize phage display libraries to select peptides that specifically bind to the mesenchymal cells that support osteoclast differentiation, determine which of the peptides regulate osteoclast differentiation, and identify the extracellular matrix/cell surface molecules that bind to these peptides. This project will provide significant new information on the extracellular matrix/cell surface molecules produced by mesenchymal cells in order to support osteoclast differentiation. This project will also identify novel peptides that specifically inhibit osteoclast differentiation and that,therefore, may be useful starting points for a peptidomimetic drug discovery program aimed at conditions of chronic bone loss.