Insulin-like growth factor II promoter expression in cultured rodent osteoblasts and adult rat bone. 1998

V Gangji, and S Rydziel, and B Gabbitas, and E Canalis
Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105-1299, USA.

Insulin-like growth factor (IGF)-II stimulates bone formation by increasing the replication of cells of the osteoblastic lineage and by enhancing the differentiated function of the osteoblast. Although IGF-II is synthesized by skeletal cells, little is known about the mechanisms involved and its regulation by growth factors. IGF-II expression is tissue specific and is developmentally regulated. In the present study, we examined the expression of IGF-II in fetal rat, newborn mouse and MC3T3-E1 osteoblastic (Ob) cells, and in adult rat calvariae. We also determined mechanisms involved in the regulation of IGF-II by platelet-derived growth factor (PDGF) BB, fibroblast growth factor-2 (FGF-2), and transforming growth factor (TGF) beta1. Northern analysis revealed IGF-II transcripts of 3.6 and 1.2 kb in osteoblastic cells and adult rat calvariae. Ribonuclease (RNase) protection assay using probes specific to the three known IGF-II promoters, P1, P2, and P3, demonstrated messenger RNA (mRNA) expression driven by P3 in osteoblasts and adult rat calvariae, but no expression of P1 or P2 transcripts. PDGF BB, FGF-2, and TGF beta1 inhibited the expression of IGF-II P3 mRNA by 50%. PDGF BB, FGF-2, and TGF beta1 also decreased the rates of IGF-II transcription in rat Ob cells as determined by nuclear run-on assays and did not modify the decay of IGF-II in transcriptionally arrested rat Ob cells. In conclusion, the synthesis of IGF-II in osteoblastic cells and in adult rat calvariae is driven by IGF-II P3 and is regulated by skeletal growth factors acting at the transcriptional level using the IGF-II P3.

UI MeSH Term Description Entries
D007335 Insulin-Like Growth Factor II A well-characterized neutral peptide believed to be secreted by the LIVER and to circulate in the BLOOD. It has growth-regulating, insulin-like and mitogenic activities. The growth factor has a major, but not absolute, dependence on SOMATOTROPIN. It is believed to be a major fetal growth factor in contrast to INSULIN-LIKE GROWTH FACTOR I, which is a major growth factor in adults. IGF-II,Multiplication-Stimulating Activity,Somatomedin MSA,IGF-2,Insulin Like Growth Factor II,Insulin-Like Somatomedin Peptide II,Multiplication-Stimulating Factor,Somatomedin A,Factor, Multiplication-Stimulating,Insulin Like Somatomedin Peptide II,Multiplication Stimulating Activity,Multiplication Stimulating Factor
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
D011401 Promoter Regions, Genetic DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes. rRNA Promoter,Early Promoters, Genetic,Late Promoters, Genetic,Middle Promoters, Genetic,Promoter Regions,Promoter, Genetic,Promotor Regions,Promotor, Genetic,Pseudopromoter, Genetic,Early Promoter, Genetic,Genetic Late Promoter,Genetic Middle Promoters,Genetic Promoter,Genetic Promoter Region,Genetic Promoter Regions,Genetic Promoters,Genetic Promotor,Genetic Promotors,Genetic Pseudopromoter,Genetic Pseudopromoters,Late Promoter, Genetic,Middle Promoter, Genetic,Promoter Region,Promoter Region, Genetic,Promoter, Genetic Early,Promoter, rRNA,Promoters, Genetic,Promoters, Genetic Middle,Promoters, rRNA,Promotor Region,Promotors, Genetic,Pseudopromoters, Genetic,Region, Genetic Promoter,Region, Promoter,Region, Promotor,Regions, Genetic Promoter,Regions, Promoter,Regions, Promotor,rRNA Promoters
D001842 Bone and Bones A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principal cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX. Bone Tissue,Bone and Bone,Bone,Bones,Bones and Bone,Bones and Bone Tissue,Bony Apophyses,Bony Apophysis,Condyle,Apophyses, Bony,Apophysis, Bony,Bone Tissues,Condyles,Tissue, Bone,Tissues, Bone
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
D000077214 Becaplermin A recombinant human platelet-derived growth factor B-chain dimer used to promote WOUND HEALING by stimulating PHYSIOLOGIC ANGIOGENESIS. PDGF-BB,Platelet-Derived Growth Factor BB,Platelet-Derived Growth Factor BB, Recombinant,Recombinant Platelet-Derived Growth Factor BB,Regranex,rPDGF-BB,rhPDGF-BB,Platelet Derived Growth Factor BB,Platelet Derived Growth Factor BB, Recombinant,Recombinant Platelet Derived Growth Factor BB
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
D000831 Animals, Newborn Refers to animals in the period of time just after birth. Animals, Neonatal,Animal, Neonatal,Animal, Newborn,Neonatal Animal,Neonatal Animals,Newborn Animal,Newborn Animals
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

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