The overall goal of the research is study the interactions between macromolecules of the cartilaginous matrix and to understand how these macromolecular interactions influence morphogenetic processes during the development of the embryonic limb. Specifically, we will investigate link protein (LP) and cartilage matrix protein (CMP) during limb morphogenesis. In cartilage, LP forms a ternary complex with aggrecan and hyaluronic acid (HA) and stabilizes the aggrecan-HA interactions. CMP is a molecular marker for post-mitotic chondrotytes and associates with the collagen fibril in cartilage. These two molecules have very different patterns of expression. LP is ubiquitously expressed and the expression of CMP is restricted to cartilage. In the growth plate of the long bones the LP gene is transcribed in both the zones of proliferation and maturation, whereas transcription of the CMP gene occurs only in the zone of maturation. We will use transgenic approaches to test several hypotheses that are based on our biochemical data. The transgenic approach to be used is the replication competent avian retrovirus with which transgenes will be delivered to chondrocytes in culture and in the intact embryo. The role of CMP will be evaluated on chondrocyte proliferation, matrix establishment and skeletal development. The role of LP in the establishment and maintenance of the integrity of the extracellular matrix will be investigated.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD022016-15
Application #
2883122
Study Section
Pathobiochemistry Study Section (PBC)
Program Officer
Lymn, Richard W
Project Start
1996-03-01
Project End
2001-02-28
Budget Start
1999-03-01
Budget End
2001-02-28
Support Year
15
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
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