Gene Regulation and Function of Cartilage

软骨是一种高度特化的结缔组织，具有独特的形态和生化特征。 它含有广泛的细胞外基质，并提供机械强度以抵抗关节中的压缩。 在发育过程中，软骨作为大多数骨骼生长和发育的模板。 当软骨形成受损时，四肢、颅面骨和无骨骨骼的骨骼畸形发生。 软骨细胞产生大量软骨特异性基质分子，包括II型胶原、聚集蛋白聚糖、连接蛋白和透明质酸。软骨发育是由间充质细胞凝聚形成原始软骨，然后是软骨细胞成熟而启动的。 这些包括静止、增殖、肥大前和肥大软骨细胞。 作为软骨内骨形成的最后一步，肥大的软骨被血管和骨祖细胞侵入，钙化的软骨随后被骨取代。 因此，软骨细胞分化的空间和时间调节在决定骨骼组成部分的长度和宽度方面是必不可少的。激素和维生素通过调节基因的转录来影响软骨的发育和成熟。 我们的目标是确定激活软骨细胞特异性基因的机制，并阐明软骨发育的分子基础。利用动物模型，我们还研究了软骨蛋白在体内的功能。 我们启动了口腔和颅面基因组解剖计划（OC-GAP），以确定对牙齿和颅面发育重要的新基因。 我们的目标是发现和表征以前未知的基因，以帮助了解牙齿和颅面组织如何发育，并确定这些组织或口腔癌异常的分子缺陷。口、颈和头部的颅面畸形是公众主要关注的问题。 大量的基因与这些异常和癌症有关。作为第一步，我们已经开始识别和编目涉及牙齿和颅面发育特定阶段的基因。 具有高度位置和阶段特异性表达的基因的鉴定是重要的，因为基因产物可能在颅面组织的形成中具有关键作用。 还预计这些基因的突变会导致异常。 这些信息也将有助于生产诊断试剂，开发疾病和出生缺陷预防方法，以及潜在的基因疗法。

Cartilage is a highly specialized connective tissue with distinct morphological and biochemical characteristics. It contains an extensive extracellular matrix and provides mechanical strength to resist compression in joints. In development, cartilage serves as the template for the growth and development of most bones. When cartilage formation is impaired, skeletal malformation of the limbs, craniofacial bones, and appendicular skeleton occurs. Chondrocytes produce large amounts of cartilage-specific matrix molecules, including type II collagen, aggrecan, link protein, and hyaluronan. Cartilage development is initiated by mesenchymal cell condensation to form primordial cartilage followed by chondrocyte maturation. These include resting, proliferative, prehypertrophic, and hypertrophic chondrocytes. As a final step in endochondral bone formation, hypertrophic cartilage is invaded by blood vessels and osteoprogenitor cells, and the calcified cartilage is subsequently replaced by bone. Thus, spatial and temporal regulation of chondrocyte differentiation is essential in determining the length and width of skeletal components. Hormones and vitamins affect cartilage development and maturation by regulating the transcription of genes. Our objective is to define the mechanisms for activating chondrocyte-specific genes and to elucidate the molecular basis of cartilage development. Using an animal model, we also study the function of cartilage proteins in vivo. We initiated the Oral and Craniofacial Genome Anatomy Project (OC-GAP) to identify novel genes important for tooth and craniofacial development. Our goal is to discover and characterize previously unknown genes to help understand how tooth and craniofacial tissues develop and to define the molecular defects underlying anomalies of these tissues or oral cancer. Craniofacial anomalies of the mouth, neck, and head are of major public concern. A large number of genes are involved in such anomalies and cancers. As an initial step, we have started to identify and catalogue the genes involved in specific stages of tooth and craniofacial development. The identification of genes that have highly location- and stage-specific expression is important since the gene products are likely to have key roles in the formation of craniofacial tissues. It is also expected that mutations in these genes cause anomalies. This information will also be useful for generating diagnostic reagents, developing methods for disease and birth defect prevention, and for potential gene therapies.