Characterization and autoregulation of latent transforming growth factor β (TGFβ) complexes in osteoblast-like cell lines. Production of a latent complex lacking the latent TGFβ-binding protein

We have previously shown that bone organ cultures produce large amounts of latent transforming growth factor β (TGFβ), which lacks latent TGFβ- binding protein (LTBP). In this study we used the known osteoblast-like cell lines UMR-106, ROS 17/2.8, and MG63 as models to further examine latent TGFβ expression in bone. We found that the osteosarcoma cell line UMR-106 secreted latent TGFβ almost exclusively as a 100-kDa complex lacking LTBP. ROS 17/2.8 cells produced both the 100-kDa complex and also a 290-kDa complex containing the fibroblastic (190 kDa) form of LTBP. MG63 cells (like human foreskin fibroblasts) expressed almost exclusively the 290-kDa complex. To investigate the regulation of latent TGFβ complexes in bone cells we assessed the effects of TGFβ1 treatment on expression of active and latent TGFβ. TGFβ1 induced secretion of latent but not active TGFβ in all cell types examined. In human foreskin fibroblast cells, TGFβ1 and LTBP mRNA were expressed concomitantly. In contrast, in osteosarcoma cell lines autoinduction of TGFβ1 mRNA was associated with either a delayed increase or no change in LTBP mRNA. In UMR-106 cells LTBP message was virtually undetectable. We postulate that the expression of different latent TGFβ forms by osteoblast- like cells may reflect their maturation states and that different latent TGFβ complexes may have different functions, for example as secretory forms or as matrix storage forms.