Modulation of the Effects of Glucocorticoids on Collagen Synthesis in Fetal Rat Calvariae by Insulin-like Growth Factor Binding Protein-2

Kream, Barbara E.; Tetradis, Sotirios; LaFrancis, D; Fall, Pamela; Feyen, Jean H.M.; Raisz, Lawrence G.

doi:10.1359/jbmr.1997.12.6.889

Cited by 29 publications

(25 citation statements)

References 61 publications

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“…In contrast to our findings, several previous studies (40)(41)(42)(43) indicate that IGFBP-2 can inhibit IGF action. There are, however, important differences between these studies and our in vivo and in vitro findings.…”

Section: Discussioncontrasting

confidence: 99%

Insulin-like growth factor system abnormalities in hepatitis C-associated osteosclerosis. Potential insights into increasing bone mass in adults.

et al. 1998

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Hepatitis C-associated osteosclerosis (HCAO) is a rare disorder characterized by a marked increase in bone mass during adult life. Despite the rarity of HCAO, understanding the mediator(s) of the skeletal disease is of great interest. The IGFs-I and -II have potent anabolic effects on bone, and alterations in the IGFs and/or IGF-binding proteins (IGFBPs) could be responsible for the increase in bone formation in this disorder. Thus, we assayed sera from seven cases of HCAO for IGF-I, IGF-II, IGF-IIE (an IGF-II precursor), and IGFBPs. The distribution of the serum IGFs and IGFBPs between their ternary ( ‫ف‬ 150 kD) and binary ( ‫ف‬ 50 kD) complexes was also determined to assess IGF bioavailability.HCAO patients had normal serum levels of IGF-I and -II, but had markedly elevated levels of IGF-IIE. Of the IGFBPs, an increase in IGFBP-2 was unique to these patients and was not found in control hepatitis C or hepatitis B patients. IGF-I and -II in sera from patients with HCAO were carried, as in the case of sera from control subjects, bound to IGFBP-3 in the ‫ف‬ 150-kD complex, which is retained in the circulation. However, IGF-IIE was predominantly in the ‫ف‬ 50-kD complex in association with IGFBP-2; this complex can cross the capillary barrier and access target tissues. In vitro, we found that IGF-II enhanced by over threefold IGFBP-2 binding to extracellular matrix produced by human osteoblasts and that in an extracellular matrix-rich environment, the IGF-II/IGFBP-2 complex was as effective as IGF-II alone in stimulating human osteoblast proliferation. Thus, IGFBP-2 may facilitate the targeting of IGFs, and in particular IGF-IIE, to skeletal tissue in HCAO patients, with a subsequent stimulation by IGFs of osteoblast function. Our findings in HCAO suggest a possible means to increase bone mass in patients with osteoporosis. (

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Section: Discussioncontrasting

confidence: 99%

Insulin-like growth factor system abnormalities in hepatitis C-associated osteosclerosis. Potential insights into increasing bone mass in adults.

et al. 1998

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“…In this context, we found that C/EBP8 and C/EBPI3 were both induced by transient exposure to low doses of glucocorticoid, and in so doing, increased new IGF-I gene expression in response to agents that generate cAMP In contrast, continuous treatment with highdose glucocorticoid directly suppressed IGF-I mRNA expression. The latter result appears to occur at a point downstream of new C/EBP synthesis, through a mechanism that blocks or perhaps supersedes the stimulatory effect of cAMP on C/EBP activity (McCarthy et al, 1990a(McCarthy et al, , 2000Kream et al, 1997). These findings thus suggest that IGF-I, and perhaps other target genes for C/EBPs, may partly account for permissive effects on skeletal tissue integrity that are related to normal physiological variations in serum glucocorticoid (Fig.…”

Section: (I) the Situationsmentioning

confidence: 82%

Links Among Growth Factors, Hormones, and Nuclear Factors With Essential Roles in Bone Formation

McCarthy

Centrella

2000

Critical Reviews in Oral Biology & Medicine

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Research performed during the last several years implicates important roles for a variety of growth factors that affect osteoblasts or their precursors during bone development, remodeling, or repair. Of these, three families of growth factors in particular-the transforming growth factor betas (TGF-fs), insulin-like growth factors (IGFs), and bone morphogenetic proteins (BMPs)-are considered to be principal local regulators of osteogenesis, although none is specific for cells of the osteoblast lineage. Therefore, mechanisms to induce skeletal tissue specificity might occur through interactions among these growth factors, with circulating hormones, or through specific intracellular mediators. In the latter case, even more recent studies point to two nuclear transcription factors, termed Core Binding Factor a 1 (CBFa 1) and CCAAT/Enhancer Binding Protein 8 (C/EBP8), as significant regulators of the expression or activity of specific bone growth factors or their receptors. Perhaps more importantly, events that link these growth factors to nuclear proteins occur in response to glucocorticoids, sex steroids, parathyroid hormone (PTH), or prostaglandin E2 (PGE2), which themselves have wellknown effects on bone biology. In this review, we discuss the situations and processes that initially suggested growth-factor-and hormone-specific interactions on cells within the osteoblast lineage, and present evidence for roles that CBFal and C/EBP6 have on osteoblast function. Finally, we offer examples for how these factors integrate events that are associated with various aspects of bone formation.

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“…Experiments using organ cultures of fetal or neonatal bone have shown that exposure to glucocorticoids increases collagen synthesis and alkaline phosphatase activityparameters of osteoblast differentiation -after 24 h of culture, but decreases these parameters after 96 h (Dietrich et al 1979, Canalis 1983, Kream et al 1997. In addition, both stimulation and inhibition of cell proliferation by glucocorticoids have been reported in these organ cultures (Tenenbaum & Heersche 1985, McCulloch & Tenenbaum 1986, Kream et al 1997. In isolated osteoblast-like cell populations, glucocorticoids decrease cell proliferation but increase alkaline phosphatase activity (Chen et al 1977, Wong et al 1990, Cheng et al 1994.…”

Section: Introductionmentioning

confidence: 99%

“…They appear to depend upon whether physiological or pharmacological concentrations of the hormone are used, on the time and duration of exposure to the drug, and on the particular system investigated (Bellows et al 1987). Experiments using organ cultures of fetal or neonatal bone have shown that exposure to glucocorticoids increases collagen synthesis and alkaline phosphatase activityparameters of osteoblast differentiation -after 24 h of culture, but decreases these parameters after 96 h (Dietrich et al 1979, Canalis 1983, Kream et al 1997. In addition, both stimulation and inhibition of cell proliferation by glucocorticoids have been reported in these organ cultures (Tenenbaum & Heersche 1985, McCulloch & Tenenbaum 1986, Kream et al 1997.…”

Section: Introductionmentioning

confidence: 99%

Effects of dexamethasone on proliferation, activity, and cytokine secretion of normal human bone marrow stromal cells: possible mechanisms of glucocorticoid-induced bone loss

Sl²,

Gs³

1999

Journal of Endocrinology

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It is well documented that glucocorticoid excess causes bone loss, but the mechanisms of these effects remain poorly defined. To understand further the mechanisms of glucocorticoid-induced osteoporosis, we investigated the effects of glucocorticoids on bone formation and bone resorption by examining the proliferation, functional activities, and cytokine secretion of cultured human bone marrow stromal cells (hBMSC). Treatment with dexamethasone for 24 h at the concentration of 10 8 M significantly suppressed [ 3 H]thymidine incorporation and further inhibition was observed with longer treatment (8 days) or higher concentration (10 7 M). Alkaline phosphatase activity of hBMSC was markedly stimulated with addition of dexamethasone (10 8 M), to 191 22% (after 4 days) and 317 46% (after 7 days) of control. Dexamethasone (10 8 M) treatment for 48 h decreased the incorporation of [ 3 H]proline into collagenasedigestible protein (CDP; 43·7 7·9% of control) and non-collagen protein (65·2 8·4% of control), with a greater effect on CDP. Northern blot analysis indicated that 1(I)-collagen mRNA level was decreased by dexamethasone to 27·6 9·0% of the control value after 1 day of exposure, and to 55·2 6·2% after 7 days. Dexamethasone markedly suppressed basal production of interleukin (IL)-6 and IL-11 and that stimulated by parathyroid hormone (PTH), IL-1 , or tumour necrosis factor-in a dose-dependent manner. These results suggest that the glucocorticoid-induced bone loss is derived at least in part via inhibition of bone formation, which includes the suppression of osteoblast proliferation and collagen synthesis. As both basal and PTH-stimulated production of IL-6 and IL-11 are decreased by dexamethasone, the increased bone resorption observed in glucocorticoidinduced osteopenia does not appear to be mediated by IL-6 or IL-11.

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Modulation of the Effects of Glucocorticoids on Collagen Synthesis in Fetal Rat Calvariae by Insulin-like Growth Factor Binding Protein-2

Abstract: To test the hypothesis that insulin-like growth factors (IGFs) play a role in the response of bone to glucocorticoids, we determined the effects of cortisol on the incorporation of

Cited by 29 publications

References 61 publications

Insulin-like growth factor system abnormalities in hepatitis C-associated osteosclerosis. Potential insights into increasing bone mass in adults.

Insulin-like growth factor system abnormalities in hepatitis C-associated osteosclerosis. Potential insights into increasing bone mass in adults.

Links Among Growth Factors, Hormones, and Nuclear Factors With Essential Roles in Bone Formation

Effects of dexamethasone on proliferation, activity, and cytokine secretion of normal human bone marrow stromal cells: possible mechanisms of glucocorticoid-induced bone loss

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