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. 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Intramural Research (Z01)
Project #
1Z01DE000483-15
Application #
6814477
Study Section
(CDBR)
Project Start
Project End
Budget Start
Budget End
Support Year
15
Fiscal Year
2003
Total Cost
Indirect Cost
Name
Dental & Craniofacial Research
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Ishikawa, Masaki; Williams, Geneva L; Ikeuchi, Tomoko et al. (2016) Pannexin 3 and connexin 43 modulate skeletal development through their distinct functions and expression patterns. J Cell Sci 129:1018-30
Nakamura, Takashi; Yoshitomi, Yasuo; Sakai, Kiyoshi et al. (2014) Epiprofin orchestrates epidermal keratinocyte proliferation and differentiation. J Cell Sci 127:5261-72
Talamillo, Ana; Delgado, Irene; Nakamura, Takashi et al. (2010) Role of Epiprofin, a zinc-finger transcription factor, in limb development. Dev Biol 337:363-74
Matsunobu, Tomoya; Torigoe, Kiyoyuki; Ishikawa, Masaki et al. (2009) Critical roles of the TGF-beta type I receptor ALK5 in perichondrial formation and function, cartilage integrity, and osteoblast differentiation during growth plate development. Dev Biol 332:325-38
Tsang, Kwok Yeung; Chan, Danny; Cheslett, Deborah et al. (2007) Surviving endoplasmic reticulum stress is coupled to altered chondrocyte differentiation and function. PLoS Biol 5:e44
de Vega, Susana; Iwamoto, Tsutomu; Nakamura, Takashi et al. (2007) TM14 is a new member of the fibulin family (fibulin-7) that interacts with extracellular matrix molecules and is active for cell binding. J Biol Chem 282:30878-88
Iwamoto, Masahiro; Tamamura, Yoshihiro; Koyama, Eiki et al. (2007) Transcription factor ERG and joint and articular cartilage formation during mouse limb and spine skeletogenesis. Dev Biol 305:40-51
Matsumoto, Kazu; Kamiya, Nobuhiro; Suwan, Keittisak et al. (2006) Identification and characterization of versican/PG-M aggregates in cartilage. J Biol Chem 281:18257-63
Hozumi, Kentaro; Suzuki, Nobuharu; Nielsen, Peter K et al. (2006) Laminin alpha1 chain LG4 module promotes cell attachment through syndecans and cell spreading through integrin alpha2beta1. J Biol Chem 281:32929-40
Tamamura, Yoshihiro; Otani, Tomohiro; Kanatani, Naoko et al. (2005) Developmental regulation of Wnt/beta-catenin signals is required for growth plate assembly, cartilage integrity, and endochondral ossification. J Biol Chem 280:19185-95

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