TRANSFORMING GROWTH-FACTOR BETA-INDUCED DISSOCIATION BETWEEN VITAMIN-D RECEPTOR LEVEL AND 1,25-DIHYDROXYVITAMIN D-3 ACTION IN OSTEOBLAST-LIKE CELLS

In the present study the interaction between a locally produced factor in bone, transforming growth factor beta (TGF beta) and a systemic re gulator of bone metabolism, 1,25-dihydroxyvitamin D-3 (1,25-(OH)(2)D-3 ) was investigated. In rat (UMR 106, ROS 17/2.8) and human (MG-63) ost eoblastic cell lines and in isolated fetal rat osteoblasts TGF beta ca used a comparable increase in vitamin D receptor (VDR) level. A maximu m was observed after 6 h at 1 ng/ml TGF beta. Scatchard analysis revea led that up-regulation of VDR is due to an increase in receptor number and not to a change in affinity. This was supported by Northern blot analysis which showed a dose- and time-dependent increase in VDR mRNA by TGF beta. To assess the significance of the TGF beta-induced increa se in VDR level for 1,25-(OH)(2)D-3 effects cells were preincubated wi th TGF for 4 h (causing a 2-3-fold increase of the VDR level) and subs equently incubated with 1,25-(OH)(2)D-3 for 4 h and 24 h. TGF beta pre incubation potently inhibited subsequent 1,25-(OH)(2)D-3 stimulation o f osteocalcin production in both ROS 17/2.8 and MG-63 cells on protein as well as mRNA level. A similar inhibition by TGF beta was observed on the 1,25-(OH)(2)D-3-induced increase in osteopontin mRNA. The curre nt study demonstrates dissociation between regulation of VDR level and modulation of two 1,25-(OH)(2)D-3 biological responses by TGF beta in osteoblast-like cell lines of different origin. This dissociation sho ws that, besides interaction at VDR level also at other levels in the cell interaction(s) exist between TGF beta and 1,25-(OH)(2)D-3. Beside s, these data emphasize the potential importance of the interplay of l ocally produced factors and systemic calciotrophic hormones in the reg ulation of bone metabolism.