The Regulation of Bone Cell Differentiation and Proliferation by Transcription Factors

Abstract

One of the basic challenges in bone biology is to identify and understand the mechanisms by which specific molecules regulate cell proliferation, differentiation and cell-cell interactions between bone-forming osteoblasts and bone-resorbing osteoclasts which occur throughout life during normal modeling and remodeling. In recent years, many molecules have been identified which, through very different mechanisms of action, control the balance between formation and resorption. These include for example, cytokines, signaling molecules, receptors, systemic hormones and transcription factors, and these have been roughly mapped to the putative sites of action (Fig. 1). Indeed, each of these molecules are important since alterations in the expression of many of them form the basis of developmental bone defects, metabolic bone disease and skeletal neoplasias. It can be reasoned that the large number of factors which have been identified to date make it unlikely that a single mechanism alone will explain the molecular basis of bone remodeling. Rather, the intricate control of bone remodeling will likely be due to a combination of factors, some of which share target cells and pathways and others which interact indirectly. Thus, while the large number of factors increase the complexity of this system, they also serve to expand the number of potential targets for intervention.