Abstract

The purpose of the proposed studies is to examine the role of somatomedin in certain aspects of skeletal development and pathology.
One specific aim of these studies is to test the controversial hypothesis that the action of growth hormone (GH) on skeletal growth is mediated by somatomedin-C/Insulin-Like Growth Factor I (Sm-C/IGF-I). The cells responsible for skeletal growth are the chondrocytes of the epiphyseal growth plate. Newly developed molecular biological techniques coupled with culture, RIA, immunoinhibition, and histological techniques will be used to investigate the relationships between GH and somatomedin on growth plate chondrocytes in vitro and in vivo. A further aim is to examine the role of somatomedin in growth plate development. The growth plate is a developmental unit containing cells at various stages of maturation. The relationship between somatomedin and cellular development in the growth plate will be examined using molecular biological, immunocytochemical and culture techniques. Expanding upon these studies, an additional objective of this proposal is to explore the possibility that Sm-C/IGF-I and fibroblast growth factor play a combine role in regulating growth. This work will employ radioligand binding and cell culture techniques to investigate Sm-C/IGF-I and FGF interactions with growth plate chondrocytes in vitro. The long term objective of these studies is to help achieve a basic understanding of the mechanisms of skeletal growth and development. Only with such understanding can needed improvements in existing therapy eventually be achieved.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR031068-10
Application #
3155971
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1981-09-01
Project End
1994-09-29
Budget Start
1992-04-01
Budget End
1994-09-29
Support Year
10
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199

  Publications

Takahashi, Toshiaki; Morris, Elisabeth A; Trippel, Stephen B (2007) Bone morphogenetic protein-2 and -9 regulate the interaction of insulin-like growth factor-I with growth plate chondrocytes. Int J Mol Med 20:53-7
Madry, H; Kaul, G; Cucchiarini, M et al. (2005) Enhanced repair of articular cartilage defects in vivo by transplanted chondrocytes overexpressing insulin-like growth factor I (IGF-I). Gene Ther 12:1171-9
Madry, Henning; Emkey, Greg; Zurakowski, David et al. (2004) Overexpression of human fibroblast growth factor 2 stimulates cell proliferation in an ex vivo model of articular chondrocyte transplantation. J Gene Med 6:238-45
Madry, Henning; Cucchiarini, Magali; Stein, Ute et al. (2003) Sustained transgene expression in cartilage defects in vivo after transplantation of articular chondrocytes modified by lipid-mediated gene transfer in a gel suspension delivery system. J Gene Med 5:502-9
Madry, Henning; Cucchiarini, Magali; Terwilliger, Ernest F et al. (2003) Recombinant adeno-associated virus vectors efficiently and persistently transduce chondrocytes in normal and osteoarthritic human articular cartilage. Hum Gene Ther 14:393-402
Madry, Henning; Padera, Robert; Seidel, Joachim et al. (2002) Gene transfer of a human insulin-like growth factor I cDNA enhances tissue engineering of cartilage. Hum Gene Ther 13:1621-30
Bonassar, L J; Grodzinsky, A J; Frank, E H et al. (2001) The effect of dynamic compression on the response of articular cartilage to insulin-like growth factor-I. J Orthop Res 19:11-7
Madry, H; Zurakowski, D; Trippel, S B (2001) Overexpression of human insulin-like growth factor-I promotes new tissue formation in an ex vivo model of articular chondrocyte transplantation. Gene Ther 8:1443-9
Madry, H; Trippel, S B (2000) Efficient lipid-mediated gene transfer to articular chondrocytes. Gene Ther 7:286-91
Bonassar, L J; Grodzinsky, A J; Srinivasan, A et al. (2000) Mechanical and physicochemical regulation of the action of insulin-like growth factor-I on articular cartilage. Arch Biochem Biophys 379:57-63

Showing the most recent 10 out of 25 publications