Overexpression of insulin-like growth factor binding protein-5 decreases osteoblastic function in vitro.
Skeletal cells synthesize insulin-like growth factors (IGF) and their binding proteins (IGFBP). The effects of IGFBP-5 on bone cell growth and osteoblastic function are controversial, and transgenic mice overexpressing IGFBP-5 exhibit osteopenia. The mechanisms were not explored, and in this study, we investigated the effects of IGFBP-5 overexpression in MC3T3 cells in vitro. MC3T3 cells were transduced with a retroviral vector (pLPCX) or a vector directing IGFBP-5 transcription under the control of a constitutive promoter. Untreated MC3T3 cells expressed alkaline phosphatase, and osteocalcin mRNA 1 week after confluence and at 4 weeks of culture they formed mineralized nodules. IGFBP-5 overexpression delayed the appearance of alkaline phosphatase and osteocalcin mRNA, decreased type I collagen and osteopontin mRNA and alkaline phosphatase activity (APA), and inhibited the formation of mineralized nodules. IGFBP-5 caused a modest stimulation of DNA synthesis. In conclusion, overexpression of IGFBP-5 decreases osteoblastic function possibly by binding IGFs in the bone microenvironment.
Durant
D
D
Department of Research, Saint Francis Hospital and Medical Center, Hartford, CT 06105-1299, USA.
Pereira
R M R
RM
Canalis
E
E
D016475:3T3 Cells; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002461:Cell Line, Transformed; D005786:Gene Expression Regulation / Q000502:physiology; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D011485:Protein Binding / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D014161:Transduction, Genetic
D018975:Insulin-Like Growth Factor Binding Protein 5; D012333:RNA, Messenger