Thrombospondin co-localises with TGFβ and IGF-I in the extracellular matrix of human osteoblast-like cells and is modulated by 17β estradiol

1995 ◽  
Vol 51 (3) ◽  
pp. 235-244 ◽  
Author(s):  
M. Slater ◽  
J. Patava ◽  
R. S. Mason
Keyword(s):  
Extracellular Matrix ◽  
Human Osteoblast ◽  
Igf I ◽  
17Β Estradiol

scholarly journals Age-related changes in effects of insulin-like growth factor I on human osteoblast-like cells

1997 ◽  
Vol 324 (3) ◽  
pp. 753-760 ◽  
Author(s):  
Patricia Y. d'AVIS ◽  
Chester R. FRAZIER ◽  
Jay R. SHAPIRO ◽  
Neal S. FEDARKO
Keyword(s):  
Extracellular Matrix ◽  
Steady State ◽  
Growth Factor ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Human Osteoblast ◽  
Factor I ◽  
Igf I ◽  
Age Dependent ◽  
Growth Factor I

The role of insulin-like growth factor I (IGF-I) in extracellular matrix metabolism was studied in both proliferating and confluent human osteoblast-like cultures derived from donors of different ages. In proliferating cultures, recombinant human (rh)IGF-I was found to increase the incorporation of [3H]thymidine in a dose- and age-dependent manner. To study cell proliferation dynamically, continuous growth curves with and without rhIGF-I were modelled by a modified logistic function. Increasing doses of rhIGF-I decreased the lag time and maximal growth rates, whereas plateau values decreased only at the highest dose (100 ng/ml). In post-proliferative cell strains, rhIGF-I (0.1–100 ng/ml) increased levels of type I collagen, biglycan and decorin, and to a smaller extent fibronectin and thrombospondin, whereas it decreased the levels of hyaluronan and a versican-like proteoglycan when protein and proteoglycan metabolism were followed by steady-state radiolabelling with [3H]proline, [3H]glucosamine or [35S]sulphate. These responses to rhIGF-I were found to be age-dependent, with osteoblast-like cells derived from younger patients being more responsive to rhIGF-I. When extracellular matrix turnover was analysed by pulse–chase experiments, rhIGF-I had no effect. The steady-state levels of collagen, decorin, hyaluronan and a versican-like proteoglycan for bone cells treated with rhIGF-I on day 7 in culture were equivalent to levels of these matrix components in untreated osteoblasts grown for 14 days. These results are consistent with rhIGF-I's altering cellular proliferative capacity and matrix synthesis, causing a change in the osteoblast differentiated state.

scholarly journals The Effect of HT-2 Toxin on Ovarian Steroidogenesis and Its Response to IGF-I, Leptin and Ghrelin in Rabbits

2017 ◽  
pp. 705-708 ◽  
Author(s):  
A. KOLESAROVA ◽  
N. MARUNIAKOVA ◽  
A. KADASI ◽  
M. HALENAR ◽  
M. MARAK ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fusarium Species ◽  
Endocrine System ◽  
Control Group ◽  
Trichothecene Mycotoxin ◽  
Ovarian Steroidogenesis ◽  
Estradiol Secretion ◽  
Igf I ◽  
17Β Estradiol

T-2 toxin and its metabolite HT-2 toxin are one of the most toxic mycotoxins of type A-trichothecenes, which are produced mainly by Fusarium species. Therefore, study of Fusarium toxins T-2 toxin and HT-2 toxin is an essential issue because they could also play role in failures of reproductive functions as well as endocrine system of domestic animals. Assessment of the effect of A-trichothecene mycotoxin HT-2 toxin alone or combined with insulin-like growth factor (IGF-I), leptin and ghrelin on estradiol secretion by rabbit ovarian fragments in vitro was done. Rabbit ovarian fragments were incubated without (control group) or with HT-2 toxin, or its combinations with IGF-I, leptin and ghrelin at various concentrations for 24 h. Secretion of 17β-estradiol was determined by ELISA. Firstly, HT-2 toxin at the doses 10 and 100 ng.ml-1, but not at 1 ng.ml-1 decreased 17β-estradiol secretion by ovarian fragments. Secondly, 17β-estradiol secretion was not affected by HT-2 toxin exposure combined with growth factor IGF-I, metabolic hormones leptin and ghrelin. In conclusion, HT-2 toxin has potent direct dose-dependent effects on ovarian steroidogenesis in rabbits. These direct effects of HT-2 mycotoxin on ovarian steroidogenesis could impact negatively on the reproductive performance of rabbits.

scholarly journals Glucose Regulation of Thrombospondin and Its Role in the Modulation of Smooth Muscle Cell Proliferation

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Laura A. Maile ◽  
Lee B. Allen ◽  
Christopher F. Hanzaker ◽  
Katherine A. Gollahon ◽  
Paul Dunbar ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Smooth Muscle ◽  
High Glucose ◽  
Glucose Regulation ◽  
Molecular Event ◽  
Protein Levels ◽  
Igf I ◽  
Normal Glucose ◽  
The Difference

Smooth muscle cells (SMC) maintained in high glucose are more responsive to IGF-I than those in normal glucose. There is significantly more thrombospondin-1 (TSP-1) in extracellular matrix surrounding SMC grown in 25 mM glucose. In this study we investigated 1) the mechanism by which glucose regulates TSP-1 levels and 2) the mechanism by which TS-1 enhances IGF-I signaling. The addition of TSP-1 to primary SMC was sufficient to enhance IGF-I responsiveness in normal glucose. Reducing TSP-1 protein levels inhibited IGF-I signaling in SMC maintained in high glucose. We determined that TSP-1 protected IAP/CD47 from cleavage and thereby facilitated its association with SHP substrate-1 (SHPS-1). We have shown previously that the hyperglycemia induced protection of IAP from cleavage is an important component of the ability of hyperglycemia to enhance IGF-I signaling. Furthermore we determined that TSP-1 also enhanced phosphorylation of theβ3 subunit of theαVβ3 integrin, another molecular event that we have shown are critical for SMC response to IGF-I in high glucose. Our studies also revealed that the difference in the amount of TSP-1 in the two different glucose conditions was due, at least in part, to a difference in the cellular uptake and degradation of TSP-1.

Ameliorating Glycosaminoglycan (GAG) Loss and Cell Death in Articular Cartilage Following Single-Impact Loading

2007 ◽  
Author(s):  
Roman M. Natoli ◽  
Kyriacos A. Athanasiou
Keyword(s):  
Extracellular Matrix ◽  
Cell Death ◽  
Articular Cartilage ◽  
Impact Loading ◽  
Biomechanical Properties ◽  
Cartilage Explants ◽  
Single Impact ◽  
Igf I ◽  
Post Traumatic ◽  
Bioactive Agents

Impact loading of articular cartilage leads to post-traumatic osteoarthritis (OA) through its effects on the cells and extracellular matrix (ECM) of the tissue. Studies have shown the level of impact or injurious compression correlates with increased cell death, degradation of the ECM, and detrimental changes in biomechanical properties [1]. Recently, several bioactive agents, such as P188 and IGF-I, have shown promising results by reducing cell death following injurious compression of cartilage explants [2, 3].

scholarly journals Hyperglycemia Alters the Responsiveness of Smooth Muscle Cells to Insulin-Like Growth Factor-I

Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 2435-2443 ◽  
Author(s):  
Laura A. Maile ◽  
Byron E. Capps ◽  
Yan Ling ◽  
Gang Xi ◽  
David R. Clemmons
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Mapk Pathway ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Downstream Signaling ◽  
Igf I ◽  
Cell Migration And Proliferation ◽  
Stimulation Of ◽  
In Cells

IGF-I stimulation of smooth muscle cell (SMC) migration and proliferation requires αVβ3 ligand occupancy. We hypothesized that changes in the levels of extracellular matrix proteins induced by alterations in glucose concentrations may regulate the ability of SMCs to respond to IGF-I. IGF-I stimulated migration and proliferation of SMCs that had been maintained in 25 mm glucose containing media, but it had no stimulatory effect when tested using SMCs that had been grown in 5 mm glucose. IGF-I stimulated an increase in Shc phosphorylation and enhanced activation of the MAPK pathway in SMCs grown in 25 mm glucose, whereas in cells maintained in 5 mm glucose, IGF-I had no effect on Shc phosphorylation, and the MAPK response to IGF-I was markedly reduced. In cells grown in 25 mm glucose, the levels of αVβ3 ligands, e.g. osteopontin, vitronectin, and thrombospondin, were all significantly increased, compared with cells grown in 5 mm glucose. The addition of these αVβ3 ligands to SMCs grown in 5 mm glucose was sufficient to permit IGF-I-stimulated Shc phosphorylation and downstream signaling. Because we have shown previously that αVβ3 ligand occupancy is required for IGF-I-stimulated Shc phosphorylation and stimulation of SMC growth, our data are consistent with a model in which 25 mm glucose stimulates increases in the concentrations of these extracellular matrix proteins, thus enhancing αVβ3 ligand occupancy, which leads to increased Shc phosphorylation and enhanced cell migration and proliferation in response to IGF-I.

scholarly journals 17β-Estradiol attenuates diabetic kidney disease by regulating extracellular matrix and transforming growth factor-β protein expression and signaling

2007 ◽  
Vol 293 (5) ◽  
pp. F1678-F1690 ◽  
Author(s):  
Alexis Dixon ◽  
Christine Maric
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Renal Disease ◽  
Protein Expression ◽  
Transforming Growth Factor ◽  
Disease Process ◽  
Type I ◽  
Plasminogen Activator Inhibitor 1 ◽  
Diabetic Renal Disease ◽  
17Β Estradiol

We previously showed that supplementation with 17β-estradiol (E2) from the onset of diabetes attenuates the development of diabetic renal disease. The aim of the present study was to examine whether E2 can also attenuate the disease process once it has developed. The present study was performed in nondiabetic and streptozotocin-induced diabetic Sprague-Dawley rats. E2 supplementation began after 9 wk of diabetes and continued for 8 wk. Diabetes was associated with an increase in urine albumin excretion, glomerulosclerosis, tubulointerstitial fibrosis, renal cortical collagen type I and IV, laminin, plasminogen activator inhibitor-1, tissue inhibitors of metalloproteinase-1 and -2, transforming growth factor (TGF)-β, TGF-β receptor type I and II, Smad2/3, phosphorylated Smad2/3, and Smad4 protein expression, and CD68-positive cell abundance. Decreases in matrix metalloproteinase (MMP)-2 protein expression and activity and decreases in Smad6 and Smad7 protein expression were also associated with diabetes. E2 supplementation completely or partially attenuated all these changes, except Smad4 and fibronectin, on which E2 supplementation had no effect. These data suggest that E2 attenuates the progression of diabetic renal disease once it has developed by regulating extracellular matrix, TGF-β, and expression of its downstream regulatory proteins. These findings support the notion that sex hormones in general, and E2 in particular, are important regulators of renal function and may be novel targets for the treatment and prevention of diabetic renal disease.

17β-Estradiol Inhibits Outward Voltage-Gated K+ Currents in Human Osteoblast-Like MG63 Cells

2012 ◽  
Vol 246 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Xiantao Li ◽  
Shouchao Zheng ◽  
Xuehai Dong ◽  
Jun Xiao
Keyword(s):  
Human Osteoblast ◽  
Voltage Gated ◽  
Mg63 Cells ◽  
17Β Estradiol ◽  
K Currents

scholarly journals Extracellular matrix regulates ovine granulosa cell survival, proliferation and steroidogenesis: relationships between cell shape and function

2001 ◽  
Vol 169 (2) ◽  
pp. 347-360 ◽  
Author(s):  
C Huet ◽  
C Pisselet ◽  
B Mandon-Pepin ◽  
P Monget ◽  
D Monniaux
Keyword(s):  
Extracellular Matrix ◽  
Type I Collagen ◽  
Follicular Development ◽  
Type I ◽  
Rgd Peptides ◽  
Large Follicle ◽  
Antral Follicles ◽  
Progesterone Secretion ◽  
Estradiol Secretion ◽  
Igf I

The extracellular matrix (ECM), constituting the follicular basal lamina and present also between follicular cells and in the follicular fluid, is believed to regulate granulosa cell (GC) function during follicular development. Ovine GCs isolated from small (1-3 mm in diameter) or large (4-7 mm in diameter) antral follicles were cultured on various pure ECM components (type I collagen, fibronectin, laminin), synthetic substrata enhancing (RGD peptides) or impairing (poly 2-hydroxyethylmethacrylate (poly-hema)) cell adhesion, or in the presence of heparin. The effects of these factors, used alone or in combination with IGF-I and/or FSH, were evaluated in terms of GC spread, survival, proliferation and steroidogenesis. When grown on type I collagen (CI) gel, poly-hema or heparin, GCs from both large and small follicles exhibited a round shape and a low proliferation rate. Compared with non-coated plastic substratum as a control, these ECM or synthetic compounds enhanced estradiol secretion and reduced progesterone secretion by large-follicle GCs. In contrast, GCs from both large and small follicles spread extensively on CI coating, fibronectin, laminin and RGD peptides. Fibronectin and laminin dramatically increased the proliferation rate and enhanced survival of GCs from both origins. Moreover, fibronectin, laminin and RGD peptides reduced estradiol secretion by large-follicle GCs. Unexpectedly, CI coating increased estradiol secretion and reduced progesterone secretion by large-follicle GCs, suggesting that type I collagen was able to maintain estradiol secretion independently of GC shape. Finally, GC responsiveness to IGF-I and FSH, in terms of proliferation and steroidogenesis, was generally maintained when cells were grown on ECM components, RGD peptides and in the presence of heparin. However, when large-follicle GCs were grown as non-adherent clusters (as observed on poly-hema) basal and IGF-I- and/or FSH-stimulated progesterone secretions were totally abolished. Overall, this study shows that GC shape, survival, proliferation and steroidogenesis can be modulated in vitro by pure ECM components in a specific and coordinated manner. It is suggested that, in vivo, fibronectin and laminin would sustain follicular development by enhancing the survival and proliferation of GCs, whereas type I collagen might participate in the maintenance of estradiol secretion in large antral follicles.

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