Transforming growth factor-beta1 stimulates the production of insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in human bone marrow stromal osteoblast progenitors.

TY - JOUR

T1 - Transforming growth factor-beta1 stimulates the production of insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in human bone marrow stromal osteoblast progenitors.

AU - Kveiborg, M

AU - Flyvbjerg, A

AU - Eriksen, E F

AU - Kassem, M

N1 - Keywords: Adult; Blotting, Northern; Blotting, Western; Bone Marrow Cells; Cell Culture Techniques; Cell Division; Cyclic AMP; Gene Expression Regulation; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Osteoblasts; Promoter Regions (Genetics); RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction; Stromal Cells; Trans-Activation (Genetics); Transcription, Genetic; Transforming Growth Factor beta; Transforming Growth Factor beta1

PY - 2001

Y1 - 2001

N2 - While transforming growth factor-beta1 (TGF-beta1) regulates proliferation and differentiation of human osteoblast precursor cells, the mechanisms underlying these effects are not known. Several hormones and locally acting growth factors regulate osteoblast functions through changes in the insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs). Thus, we studied the effects of TGF-beta1 on IGFs and IGFBPs in human marrow stromal (hMS) osteoblast precursor cells. TGF-beta1 increased the steady-state mRNA level of IGF-I up to 8.5+/-0.6-fold (P<0.001) in a dose- (0.1-10 ng/ml), and time-dependent (12-72 h) manner. No significant effects on IGF-II gene expression were detectable. Employing RNase protection and nuclear run-on assays, these effects on IGF-I were found to take place at the transcriptional level and were not dependent on de novo protein synthesis. Using the transient transfection of various fragments of the IGF-I promoter 1, we found that TGF-beta responsive elements were present in a promoter fragment ranging from-65 bp to+55 bp relative to the major transcription start site in exon 1. In addition, TGF-beta1 treatment resulted in a dose- and time-dependent increase (2-fold) in the IGFBP-3 steady-state mRNA level as well as in protein production but did not affect IGFBP-2 or IGFBP-4 at mRNA or protein levels. Our results indicate that TGF-beta1 exerts significant effects on stimulatory components of the IGF-system and that may represent a mechanism mediating TGF-beta effects on the biological functions of osteoblasts.

AB - While transforming growth factor-beta1 (TGF-beta1) regulates proliferation and differentiation of human osteoblast precursor cells, the mechanisms underlying these effects are not known. Several hormones and locally acting growth factors regulate osteoblast functions through changes in the insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs). Thus, we studied the effects of TGF-beta1 on IGFs and IGFBPs in human marrow stromal (hMS) osteoblast precursor cells. TGF-beta1 increased the steady-state mRNA level of IGF-I up to 8.5+/-0.6-fold (P<0.001) in a dose- (0.1-10 ng/ml), and time-dependent (12-72 h) manner. No significant effects on IGF-II gene expression were detectable. Employing RNase protection and nuclear run-on assays, these effects on IGF-I were found to take place at the transcriptional level and were not dependent on de novo protein synthesis. Using the transient transfection of various fragments of the IGF-I promoter 1, we found that TGF-beta responsive elements were present in a promoter fragment ranging from-65 bp to+55 bp relative to the major transcription start site in exon 1. In addition, TGF-beta1 treatment resulted in a dose- and time-dependent increase (2-fold) in the IGFBP-3 steady-state mRNA level as well as in protein production but did not affect IGFBP-2 or IGFBP-4 at mRNA or protein levels. Our results indicate that TGF-beta1 exerts significant effects on stimulatory components of the IGF-system and that may represent a mechanism mediating TGF-beta effects on the biological functions of osteoblasts.

M3 - Journal article

C2 - 11375125

SN - 0022-0795

VL - 169

SP - 549

EP - 561

JO - Journal of Endocrinology

JF - Journal of Endocrinology

IS - 3

ER -