Date of Award
2006
Degree Type
Thesis
Degree Name
Master of Science
Program
Physiology
Supervisor
Dr. Frank Beier
Abstract
Endochondral ossification is an intricately controlled process resulting in bone formation that is not completely understood. Recently, C-type natriuretic peptide (CNP) has been identified as a key positive regulator of endochondral bone growth in mouse models. To identify upstream and downstream factors involved in CNP signaling, both an organ culture model system and primary chondrocyte cultures were employed. It was demonstrated that the synthetic glucocorticoid dexamethasone (DEX) regulates expression of genes involved in CNP signaling; in particular, DEX increases expression of CNP itself. Concurrently, the importance of p38 MAPK activity for CNP-induced bone growth was shown through length, weight, and area measurements, along with histological evaluation. In order to generate a comprehensive image of CNP’s actions, microarray studies were undertaken on tibiae cultured in the absence and presence of CNP and micro-dissected into the resting/proliferating, hypertrophie, and mineralized zones of the bone. Bioinformatics analyses show the hypertrophic zone gene expression to be most influenced by CNP, in comparison to the other two areas. These studies potentially identify numerous novel components of CNP signaling in cartilage and provide an impetus and the basis for further exploration.
Recommended Citation
Agoston, Hanga, "C-TYPE NATRIURETIC PEPTIDE REGULATION OF ENDOCHONDRAL BONE GROWTH" (2006). Digitized Theses. 4991.
https://ir.lib.uwo.ca/digitizedtheses/4991