CONTROL OF TGF-BETA RECEPTOR EXPRESSION IN BONE

Michael Centrella, Changhua Ji, Thomas L. McCarthy

Department of Surgery, Plastic Surgery Section, Yale University School of Medicine, 333 Cedar Street, PO Box 208041, New Haven, CT 06520-8041,

Received 12/1/97 Accepted 12/5/97

2. INTRODUCTION

Transforming growth factor beta (TGF-beta) is a potent and ubiquitous growth regulator. It was first isolated from tumor extracts where it was thought to induce a "transformation" between normal and neoplastic cell growth. Since then, TGF-beta expression or its activity has been examined in essentially every tissue in the body. Surprisingly, its effects diverge considerably. Stimulatory, inhibitory, or negligible effects have been reported on the same biochemical processes, and even within cells from the same tissue lineage. Some variations relate to its release from inactive complexes, some to its concentration-dependent biphasic actions, and others to the differentiation status of target cells. Therefore, subtle control mechanisms must exist that regulate TGF-beta expression or its activity within tissues. All of these processes have also been noted in bone. Still, little is known about how the very same molecule produces such divergent effects, and especially, how these events change during tissue differentiation.

TGF-beta binding to cell surface components is altered by certain agents that activate or suppress bone cell activity. Moreover, systematic differences in the TGF-beta receptor profile can be observed between less and more differentiated bone cells, suggesting that differentiation-dependent molecular regulators must co-ordinate these transitions. In the last several years new molecular tools were developed to address these questions. As a result, work on TGF-beta receptor expression has converged with other studies demonstrating the importance of a specific nuclear factor that appears to drive osteogenesis. In this review, we describe the progression of results, obtained by us and other investigators, that revealed new insight into the control of TGF-beta receptor expression and TGF-beta activity in bone.