Abstract
In the present study the interaction between a locally produced factor in bone, transforming growth factor β (TGFβ) and a systemic regulator of bone metabolism, 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) was investigated. In rat (UMR 106, ROS 17/2.8) and human (MG-63) osteoblastic cell lines and in isolated fetal rat osteoblasts TGFβ caused a comparable increase in vitamin D receptor (VDR) level. A maximum was observed after 6 h at 1 ng/ml TGFβ. Scatchard analysis revealed 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 TGFβ. To assess the significance of the TGFβ-induced increase in VDR level for l,25-(OH)2D3 effects cells were preincubated with TGF for 4 h (causing a 2–3-fold increase of the VDR level) and subsequently incubated with l,25-(OH)2D3 for 4 h and 24 h. TGFβ preincubation potently inhibited subsequent l,25-(OH)2D3 stimulation of osteocalcin production in both ROS 17/2.8 and MG-63 cells on protein as well as mRNA level. A similar inhibition by TGFβ was observed on the 1,25-(OH)2D3-induced increase in osteopontin mRNA. The current study demonstrates dissociation between regulation of VDR level and modulation of two l,25-(OH)2D3 biological responses by TGFβ in osteoblast-like cell lines of different origin. This dissociation shows that, besides interaction at VDR level also at other levels in the cell interaction(s) exist between TGFβ and 1,25-(OH)2D3. Besides, these data emphasize the potential importance of the interplay of locally produced factors and systemic calciotrophic hormones in the regulation of bone metabolism.
| Original language | English |
|---|---|
| Pages (from-to) | 27-42 |
| Number of pages | 16 |
| Journal | Bone and Mineral |
| Volume | 26 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1994 |
Bibliographical note
Funding Information:In the present study the interaction between a locally produced factor in bone, transforming growth factor B (TGFB) and a systemic regulator of bone metabolism, 1,25-dihydroxyvitamin D3 (I,25-(OH)2D3) was investigated. In rat (UMR 106, ROS 17/2.8) and human (MG-63) osteoblastic cell lines and in isolated fetal rat osteoblasts TGF/3 caused a comparable increase in vitamin D receptor (VDR) level. A maximum was observed after 6 h at l ng/ml TGFB. Scatchard analysis revealed 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/3. To assess the significance of the TGFB-induced increase in VDR level for 1,25-(OH)2D 3 effects cells were preincubated with TGF for 4 h (causing a 2-3-fold increase of the VDR level) and subsequently incubated with 1,25-(OH)2D 3 for 4 h and 24 h. TGF/3 preincubation potently inhibited subsequent 1,25-(OH)2D 3 stimulation of osteocalcin production in both ROS 17/2.8 and MG-63 cells on protein as well as mRNA level. A similar inhibition by TGFB was observed on the 1,25-(OH)2D3-induced increase in osteopontin mRNA. The current study demonstrates dissociation between regulation of VDR level and modulation of two 1,25-(OH)2D 3 biological responses by TGF/3 in osteoblast-like cell lines of different origin. This dissociation shows that, besides interaction at VDR level also at other levels in the cell interaction(s) exist be- * Corresponding author. 1" Supported by Netherlands Organization for Scientific Research. Project no. 900-541-131.