ROLE OF SOMATOMEDIN IN SKELETAL DEVELOPMENT &PATHOLOGY

  • Trippel, Stephen, (PI)

Project: Research project

Description

The purpose of the proposed studies is to examine the role of somatomedin
in skeletal development and pathology. One specific aim of these studies
is to test the hypothesis that the action of growth hormone on skeletal
growth is mediated by somatomedin. The cells responsible for skeletal
growth are the chondrocytes of the epiphyseal growth plate. Growth plate
cell culture, organ culture, and radioligand binding studies will seek to
elucidate the effect of GH on these cells in vitro, while
stimulation/inhibition studies will seek to separate and analyze the
effects of GH and somatomedin-C (Sm-C) in vivo. A second aim is to evaluate the role of Sm-C in the regulation of physeal
chondrocyte division and maturation. Autoradiographic, cell separation,
radioligand and affinity labeling studies will address the hypothesis that
these cells differ in their response to Sm-C according to their
maturational stage. Also to be tested is the hypothesis that the growth
rate of individual physes is a function of the Sc-C binding characteristics
of their cells. Thirdly, the role of Sm-C in the normal response to injury by articular
cartilage and the question whether Sm-C can enahnce the reparative
component of this response will be addressed by in vivo, intra-articular
studies in a rabbit model for joint injury. Fourthly, the hypothesis that Sm-C plays a role in the pathophysiology of
osteoarthritis will be addressed by autoradiographic, cell isolation and
radioligand binding studies comparing normal and osteoarthritic human
cartilage. Fifthly, the possibility that certain types of dwarfism may result from
defects in Sm-C receptor interactions will be tested by radioligand binding
studies of normal and dwarf bovine physeal chondrocytes. The long term objective of these studies is to help achieve a basic
understanding of the mechanism of skeletal growth and of joint function in
health and disease. Only with such understanding can needed improvements
in existing therapy eventually be achieved.
StatusFinished
Effective start/end date9/1/818/31/87

Funding

  • National Institutes of Health

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Somatomedins
Insulin-Like Growth Factor I
Pathology
Growth Plate
Cell Separation
Chondrocytes
Joints
Somatomedin Receptors
Dwarfism
Organ Culture Techniques
Wounds and Injuries
Growth
Growth Hormone
Rabbits

ASJC

  • Medicine(all)