OSTEOBLASTIC DIFFERENTIATION IS ENHANCED BY RAPAMYCIN IN RAT OSTEOBLAST-LIKE OSTEOSARCOMA (ROS-17 2.8) CELLS/

The effects of three immunosuppressants (rapamycin, FK506 and cyclospo rin A) on the proliferation and differentiation of rat osteoblasts-lik e osteosarcoma cell line, ROS 17/2.8 (ROS) cells were examined in vitr o. All immunosuppressants showed a direct inhibition on the proliferat ion of ROS cells with different potencies. Growth inhibition by rapamy cin was stronger than that by FK506 or cyclosporin A Rapamycin caused a significant increase in alkaline phosphatase (ALP) activity and in t he expression of osteopontin and osteocalcin mRNAs. FK506 caused a mod erate increase in ALP activity and a decreased expression of osteopont in mRNA. Cyclosporin A caused a decrease in ALP activity and in the ex pression of type 1 alpha 1 collagen mRNA Our study indicates that rapa mycin directly acts on ROS cells and induces osteoblastic differentiat ion, however, the effect of FK506 and cyclosporin A is weak. Rapamycin significantly enhances the differentiation induced by 1,25(OH)(2)-vit aminD(3). (C) 1998 Academic Press.