The long-term objective of this application is to understand the molecular and cellular mechanisms underlying cartilage formation and repair. Degeneration of the joint cartilage leads to osteoarthritis (OA), the most common form of arthritis affecting middle-aged and elderly people. The cartilage loss is caused, at least in part, by the failure of chondrocytes to repair the cartilage matrix and reduced proliferative capacity of the chondrocytes. The mechanisms that regulate chondrocyte proliferation and its biosynthetic activity, however, are poorly understood. The applicant has found that Zacl, a recently characterized zinc finger protein, is predominantly localized in the developing chondrogenic tissue during mouse embryogenesis. Zacl possesses anti-proliferative activity and is a potential tumor suppressor gene, suggesting that it may have a role in regulating chondrocyte proliferation and differentiation, and cartilage gene expression. This application proposes to investigate the role of Zacl in chondrogenesis using an established in vitro model culture system for chondrocyte differentiation. The effects of over-expression and inhibition of Zacl during in vitro chondrogenesis will be studied, and the genes regulated by Zacl in chondrocyte differentiation will be investigated. These studies will provide a better understanding of regulatory factors important for cartilage formation and repair.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AR050696-01
Application #
6729826
Study Section
Special Emphasis Panel (ZAR1-RJB-A (O1))
Program Officer
Tyree, Bernadette
Project Start
2003-09-25
Project End
2005-06-30
Budget Start
2003-09-25
Budget End
2004-06-30
Support Year
1
Fiscal Year
2003
Total Cost
$78,500
Indirect Cost
Name
Thomas Jefferson University
Department
Dermatology
Type
Schools of Medicine
DUNS #
053284659
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Tsuda, Takeshi; Markova, Dessislava; Wang, Hui et al. (2004) Zinc finger protein Zac1 is expressed in chondrogenic sites of the mouse. Dev Dyn 229:340-8