Links among growth factors, hormones, and nuclear factors with essential roles in bone formation

Research performed during the last several years implicates important roles for a variety of growth factors that affect osteoblasts or their precursors during bone development, remodeling, or repair. Of these, three families of growth factors in particular-the transforming growth factor betas (TGF-betas), insulin-like growth factors (IGFs), and bone morphogenetic proteins (BMPs)-are considered to be principal local regulators of osteogenesis, although none is specific for cells of the osteoblast lineage. Therefore, mechanisms to induce skeletal tissue specificity might occur through interactions among these growth factors, with circulating hormones, or through specific intracellular mediators. In the latter case, even more recent studies point to two nuclear transcription factors, termed Core Binding Factor a1 (CBFa1) and CCAAT/Enhancer Binding Protein delta (C/EBPdelta), as significant regulators of the expression or activity of specific bone growth factors or their receptors. Perhaps more importantly, events that link these growth factors to nuclear proteins occur in response to glucocorticoids, sex steroids, parathyroid hormone (PTH), or prostaglandin E2 (PGE2), which themselves have well-known effects on bone biology. In this review, we discuss the situations and processes that initially suggested growth-factor- and hormone-specific interactions on cells within the osteoblast lineage, and present evidence for roles that CBFa1 and C/EBPdelta have on osteoblast function. Finally, we offer examples for how these factors integrate events that are associated with various aspects of bone formation.