Biomaterial Database

Growth factor regulation of insulin-like growth factor binding protein-6 expression in osteoblasts. 1997

B Gabbitas, and E Canalis

Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105, USA.

Previously we have shown that transforming growth factor beta (TGF beta) 1, basic fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) BB inhibit the synthesis of insulin-like growth factor (IGF) II, but their effects on IGF binding protein (IGFBP)-6 in osteoblast cultures are not known. IGFBP-6 binds IGF II with high affinity and prevents IGF II-mediated effects, so that a possible mode of regulating the IGF II available to bone cells would be by changing the levels of IGFBP-6. To enhance our understanding of the actions of growth factors on the IGF II axis in bone, we tested the effects of TGF beta 1, basic FGF, PDGF BB, IGF I, and IGF II on the expression of IGFBP-6 in cultures of osteoblast-enriched cells from 22 day fetal rat calvariae (Ob cells). Treatment of Ob cells with TGF beta 1 caused a time- and dose-dependent decrease in IGFBP-6 mRNA levels, as determined by Northern blot analysis. The effect was maximal after 48 h and observed with TGF beta 1 concentrations of 0.04 nM and higher. TGF beta 1 also decreased IGFBP-6 polypeptide levels in the medium, as determined by Western immunoblot analysis. Cycloheximide at 3.6 microM decreased IGFBP-6 transcripts and prevented the effect of TGF beta 1. The decay of IGFBP-6 mRNA in transcriptionally arrested Ob cells was not modified by TGF beta 1. In addition, TGF beta 1 decreased the rates of IGFBP-6 transcription as determined by a nuclear run-on assay. In contrast, basic FGF, PDGF BB, IGF I, and IGF II did not change IGFBP-6 mRNA levels in Ob cells. In conclusion, TGF beta 1 inhibits IGFBP-6 expression in Ob cells by transcriptional mechanisms. Since IGFBP-6 binds IGF II and prevents its effects on bone cells, decreased synthesis of IGFBP-6 induced by TGF beta 1 could be a local feedback mechanism to increase the amount of IGF II available in the bone microenvironment.

UI	MeSH Term	Description	Entries
D007334	Insulin-Like Growth Factor I	A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.	IGF-I,Somatomedin C,IGF-1,IGF-I-SmC,Insulin Like Growth Factor I,Insulin-Like Somatomedin Peptide I,Insulin Like Somatomedin Peptide I
D010006	Osteoblasts	Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone.	Osteoblast
D010982	Platelet-Derived Growth Factor	Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication.	Platelet Derived Growth Factor,Factor, Platelet-Derived Growth,Growth Factor, Platelet-Derived
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012333	RNA, Messenger	RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.	Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D014158	Transcription, Genetic	The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.	Genetic Transcription
D015870	Gene Expression	The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.	Expression, Gene,Expressions, Gene,Gene Expressions
D016212	Transforming Growth Factor beta	A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.	Bone-Derived Transforming Growth Factor,Platelet Transforming Growth Factor,TGF-beta,Milk Growth Factor,TGFbeta,Bone Derived Transforming Growth Factor,Factor, Milk Growth,Growth Factor, Milk
D016222	Fibroblast Growth Factor 2	A single-chain polypeptide growth factor that plays a significant role in the process of WOUND HEALING and is a potent inducer of PHYSIOLOGIC ANGIOGENESIS. Several different forms of the human protein exist ranging from 18-24 kDa in size due to the use of alternative start sites within the fgf-2 gene. It has a 55 percent amino acid residue identity to FIBROBLAST GROWTH FACTOR 1 and has potent heparin-binding activity. The growth factor is an extremely potent inducer of DNA synthesis in a variety of cell types from mesoderm and neuroectoderm lineages. It was originally named basic fibroblast growth factor based upon its chemical properties and to distinguish it from acidic fibroblast growth factor (FIBROBLAST GROWTH FACTOR 1).	Basic Fibroblast Growth Factor,Fibroblast Growth Factor, Basic,HBGF-2,Cartilage-Derived Growth Factor,Class II Heparin-Binding Growth Factor,FGF-2,FGF2,Fibroblast Growth Factor-2,Heparin-Binding Growth Factor Class II,Prostate Epithelial Cell Growth Factor,Prostatropin,Cartilage Derived Growth Factor,FGF 2