REGULATION AND FUNCTIONAL ANALYSIS OF TYPE X COLLAGEN

这项提案的主要目标是研究监管和 短链亚家族成员X型胶原的功能 胶原蛋白，在哺乳动物骨骼系统的发育过程中。 在软骨内骨化(EO)过程中，软骨细胞经历了一系列 包括增殖、成熟、肥大和死亡在内的过渡。 在此过程中细胞外基质蛋白的沉积 调控的分化途径导致产生 肥大的软骨，形成钙化和骨骼的基质 证词。X型胶原蛋白在血管内皮细胞中大量表达 肥大的软骨细胞提示这种基质蛋白在 在骨骼形成中起关键作用。最近的发现支持这一观点， 然而，该分子在哺乳动物体内的真实功能 骨骼发育尚不清楚。 我们对解决哺乳动物骨骼的基本问题很感兴趣 以X型胶原蛋白为中心的发育。基因是怎么回事 激活了吗？这种基质蛋白在体内所需的功能是什么 发展？X型胶原蛋白的异常产生是如何导致的 在疾病中？野生型蛋白的异位表达会导致疾病吗？ 我们建议在体内进行基因实验来回答这些问题。的确， 我们已经培育出X型胶原蛋白缺失的小鼠。突变的动物 使我们能够直接研究这种细胞外的需求 哺乳动物骨骼系统发育过程中的基质蛋白。 从我们的提案研究中产生的信息应提供 关于X型胶原蛋白调节和功能的基本信息。

The primary objective of this proposal is to study the regulation and function of type X collagen, a member of a subfamily of short chain collagens, during the development of the mammalian skeletal system. During endochondral ossification (EO), chondrocytes undergo a series of transitions including proliferation, maturation, hypertrophy, and death. Deposition of extracellular matrix proteins during this precisely regulated differentiation pathway results in the production of hypertrophic cartilage that forms the substrate for calcification and bone deposition. Type X collagen is expressed abundantly and specifically in hypertrophic chondrocytes suggesting that this matrix protein plays a critical role in skeletal formation. Recent findings support this idea, however the true in vivo function of this molecule during mammalian skeletal development is unknown. We are interested in addressing basic questions in mammalian skeletal development that center around type X collagen. How is the gene activated? What is this matrix protein's required function during development? How does the production of abnormal type X collagen result in disease? Does ectopic expression of wild-type protein lead to disease? We propose genetic experiments in vivo to answer these questions. Indeed, we have already generated type X collagen-null mice. The mutant animals have allowed us to directly study the requirement of this extracellular matrix protein during the development of the mammalian skeletal system. The information generated from our proposal studies should provide fundamental information about type X collagen regulation and function.