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

Cyclosporin-A (CsA) inhibits in vitro proliferation of non-human tumour-cloned osteoblasts. Our aims were to study the direct effect of CsA on proliferation of normal human osteoblast (NHOb) cultures and to ascertain whether CsA-treated patients' sera (CsATPS) may exert effects on the osteoblast which differ from the direct effects of CsA. We studied 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 the addition of 20% fetal calf serum (FCS) or 20% normal human serum (NHS), (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]thymidine uptake from 2400 ng/ml for cultures with FCS and 4800 ng/ml for cultures with NHS, in (c) CsATPS produced [H-3]thymidine uptake inhibition compared with NHS. Conclusion: CsA alone inhibited [H-3]thymidine incorporation in NHOb from concentrations similar to therapeutic concentrations. With FCS or NHS, inhibition was produced at higher concentrations. CsATPS inhibited at CsA concentrations lower than those of the two previous experiments.