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

4. BONE GROWTH REGULATORS

Bone cells are regulated by systemic (hormone) and local (bone-derived) factors (4-6). Hormonal effects are well appreciated, but local bone growth factors have only been identified and characterized in the last dozen years. By mass, bone is the largest reservoir of growth factors in the body (5-8). Many local bone growth factors are synthesized by osteoblasts. Also, bone matrix is a tenacious substrate, and some matrix-bound growth factors may originate from other tissues and produce important local actions after their release from remodeling bone. Initial efforts in this field described direct effects by local growth factors on bone cell activity. Other studies then centered on interactions that occur between systemic and local factors (9-19 among many others). Studies with fetal rat bone cultures first demonstrated TGF-beta in skeletal tissue. Cells derived from rat calvariae were then used to visualize TGF-beta receptors on bone cells (reviewed previously in reference 20). This culture model also provided the first evidence for detrimental effects by glucocorticoid on TGF-beta binding and function in any tissue, and new information for specific variations in TGF-beta receptors in parallel with expression of the osteoblast phenotype (19,21). Results from these and other similar in vitro studies therefore began to predict that the effects of some bone growth regulators could converge with those induced by TGF-beta, perhaps in large part by changing the levels of specific TGF-beta receptors.