Human skeletal growth factor: characterization of the mitogenic effect on bone cells in vitro

Vascular endothelial growth factor (VEGF) is a secreted protein that is a specific growth factor for endothelial cells. We have recently demonstrated that nitric oxide (NO) donors and vasoactive peptides promoting NO-mediated vasorelaxation induce angiogenesis in vivo as well as endothelial cell growth and motility in vitro; in contrast, inhibitors of NO synthase suppress angiogenesis. In this study we investigated the role of NO in mediating the mitogenic effect of VEGF on cultured microvascular endothelium isolated from coronary postcapillary venules. VEGF induced a dose-dependent increase in cell proliferation and DNA synthesis. The role of NO was determined by monitoring proliferation or guanosine 3',5'-cyclic monophosphate (cGMP) levels in the presence and absence of NO synthase blockers. The proliferative effect evoked by VEGF was reduced by pretreatment of the cells with NO synthase inhibitors. Exposure of the cells to VEGF induced a significant increment in cGMP levels. This effect was potentiated by superoxide dismutase addition and was abolished by NO synthase inhibitors. VEGF stimulates proliferation of postcapillary endothelial cells through the production of NO and cGMP accumulation.

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Differential regulation of insulin‐like growth factor binding protein (IGFBP)‐2 mRNA in liver and bone cells by insulin and retinoic acid in vitro

FEBS Letters ◽

10.1016/0014-5793(92)80520-q ◽

1992 ◽

Vol 303 (2-3) ◽

pp. 205-209 ◽

Cited By ~ 31

Keyword(s):

Retinoic Acid ◽

Growth Factor ◽

Bone Cells ◽

Binding Protein ◽

Differential Regulation ◽

Factor Binding

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Purification of a skeletal growth factor from human bone

Biochemistry ◽

10.1021/bi00257a037 ◽

1982 ◽

Vol 21 (14) ◽

pp. 3502-3507 ◽

Cited By ~ 93

Author(s):

John R. Farley ◽

David J. Baylink

Keyword(s):

Growth Factor ◽

Human Bone ◽

Skeletal Growth ◽

Skeletal Growth Factor

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Increased serum and bone matrix levels of transforming growth factor β1 in patients with GH deficiency in response to GH treatment

Acta Endocrinologica ◽

10.1530/eje-11-0442 ◽

2011 ◽

Vol 165 (3) ◽

pp. 393-400 ◽

Cited By ~ 3

Author(s):

Thor Ueland ◽

Tove Lekva ◽

Kari Otterdal ◽

Tuva B Dahl ◽

Nicoleta Cristina Olarescu ◽

...

Keyword(s):

Growth Factor ◽

Cortical Bone ◽

Transforming Growth Factor ◽

Bone Cells ◽

Gh Deficiency ◽

Bone Matrix ◽

Transforming Growth Factor Β1 ◽

Gh Treatment

ObjectivePatients with adult onset GH deficiency (aoGHD) have secondary osteoporosis, which is reversed by long-term GH substitution. Transforming growth factor β1 (TGFβ1 or TGFB1) is abundant in bone tissue and could mediate some effects of GH/IGFs on bone. We investigated its regulation by GH/IGF1in vivoandin vitro.Design and methodsThe effects of GH substitution (9–12 months, placebo controlled) on circulating and cortical bone matrix contents of TGFβ1 were investigated in patients with aoGHD. The effects of GH/IGF1 on TGFβ1 secretion in osteoblasts (hFOB), adipocytes, and THP-1 macrophages as well as the effects on release from platelets were investigatedin vitro.ResultsIn vivoGH substitution increased TGFβ1 protein levels in cortical bone and serum.In vitro, GH/IGF1 stimulation induced a significant increase in TGFβ1 secretion in hFOB. In contrast, no major effect of GH/IGF1 on TGFβ1 was found in adipocytes and THP-1 macrophages. Finally, a minor modifying effect on SFLLRN-stimulated platelet release of TGFβ1 was observed in the presence of IGF1.ConclusionGH substitution increases TGFβ1in vivoandin vitro, and this effect could contribute to improved bone metabolism during such therapy, potentially reflecting direct effect of GH/IGF1 on bone cells.

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