Date of Award

2004

Degree Type

Thesis

Degree Name

Master of Science

Program

Physiology

Supervisor

Dr. Frank Beier

Abstract

Most of the human skeleton forms through a process known as endochondral ossification, that requires the coordinated interplay of many factors to control cartilage morphogenesis. Disturbances in this process frequently cause malformations of cartilage resulting in diseases such as osteoarthritis or chondrodysplasias. Recent studies have identified C-type natriuretic peptide (CNP) as a stimulator of cartilage growth and subsequent endochondral bone development, but the cellular and molecular mechanisms used by CNP remain largely unknown. This project studied the role of CNP in chondrogenesis and the activity of mitogen-activated protein (MAP) kinases as mediators of CNP signaling in chondrocytes. We demonstrated that CNP and cyclic guanosine monophosphate (cGMP) reproducibly enhance chondrogenesis. CNP and cGMP increase bone length in organ cultures of fetal mouse tibias, and we suggest the involvement of p38 MAP kinase and ERK1/2 in CNP signaling. These findings will contribute to the development of novel strategies for treating skeletal diseases such as osteoarthritis.

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