Variable expression der TGF-β-Rezeptoren auf humanen Osteoblasten. Ein regulationsprinzip im knochenstoffwechsel

High concentrations of transforming growth factor β (TGF-β) are found in bone matrix reflecting a pivotal role of this growth factor in the coupling of bone resorption and formation. The biological TGF-β effect is transmitted by the specific transmembrane receptors (TβR) type I and II, while TβR-III (betaglycan) is not directly involved in signal transduction. We studied the cell surface expression of TβR-I, -II and -III on 22 different human osteoblast-like cell populations by affinity crosslinking, immunoblotting and RT-PCR. Binding studies with ¹²⁵I-TGF-β1 allowed the determination of receptor number per cell and receptor affinity. All cell populations showed the presence of all three receptor types with similar relative amounts. TβR-II showed a splice variant with a 75 bp insertion in the extracellular part of the receptor. The receptor number increased with age, and osteoblasts from patients with osteogenesis imperfecta showed a higher receptor number compared to age matched controls. Furthermore, our studies demonstrated a marked ligand-induced downregulation of TGF-β receptors on human osteoblast-like cells without any evidence for recovery within the first 24h both in the presence and after the removal of the ligand. The results show a marked quantitative variability of the expression of TGF-β-receptors on human osteoblast-like cells. This regulation of the TGF-β responsiveness represents a control mechanism of the biological effect of TGF-β in addition to the complex activation mechanisms of this growth factor. Disturbances of this regulatory mechanisms may play a role in the clinical expression of bone diseases.