EFFECT OF CYCLOSPORINE-A ON NORMAL HUMAN OSTEOBLASTS IN-VITRO

Cyclosporin-A (CsA) inhibits in vitro proliferation of non-human tumou r-cloned osteoblasts. Our aims were to study the direct effect of CsA on proliferation of normal human osteoblast (NHOb) cultures and to asc ertain whether CsA-treated patients' sera (CsATPS) may exert effects o n the osteoblast which differ from the direct effects of CsA. We studi ed tritiated thymidine ([H-3]thymidine) incorporation in NHOb cultures incubated with (a) increasing CsA concentrations (1.2 to 4800 ng/ml), (bf the same concentrations as in the previous experiment but with th e addition of 20% fetal calf serum (FCS) or 20% normal human serum (NH S), (c) 40% NHS or 40% CsATPS. Results at 96 h in (a) CsA inhibited [H -3]thymidine uptake from 300 ng/ml, in fb) CsA inhibited [H-3]thymidin e uptake from 2400 ng/ml for cultures with FCS and 4800 ng/ml for cult ures with NHS, in (c) CsATPS produced [H-3]thymidine uptake inhibition compared with NHS. Conclusion: CsA alone inhibited [H-3]thymidine inc orporation in NHOb from concentrations similar to therapeutic concentr ations. With FCS or NHS, inhibition was produced at higher concentrati ons. CsATPS inhibited at CsA concentrations lower than those of the tw o previous experiments.