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  • Print publication year: 2000
  • Online publication date: June 2011

9 - Molecular genetic analysis of growth factor signaling in bone

Summary

Introduction

Disorders of bone and cartilage metabolism, including osteoporosis and osteoarthritis, are amongst the leading causes of morbidity and mortality in our aging population. These disorders account not only for a tremendous outlay in health care costs, but also compromise the quality of life of a large percentage of the world's population. Recent advances in human and murine molecular genetics have identified many of the phylogenetically conserved proteins that regulate the related processes of bone development, fracture repair and bone remodeling. They include multifunctional growth factors and morphogens, their high affinity receptors, transcription factors, and target genes including the bone morphogenetic proteins. In the mouse, these signaling components are expressed in a time-dependent manner, and in spatially restricted patterns, in developing bones, in fracture callus and in adult bone, where they co-ordinate the passage of skeletal cells through stages of replication, maturation and apoptotic cell death. Despite recent advances, little is known about the way in which individual components interact with one another to co-ordinate bone growth and bone remodeling. One particularly powerful approach to this problem is to analyze mice with a congenital deficiency of one or more of the regulatory genes, to determine if their protein products are redundant or complementary in their effect on cartilage and bone cells.