Insulin-like growth factor binding proteins (IGF-BPs) in bovine articular and ovine growth-plate chondrocyte cultures: their regulation by IGFs and modulation of proteoglycan synthesis

Sunic, Damir; Belford, David A.; McNeil, Julian; Wiebkin, Ole W.

doi:10.1016/0304-4165(95)00076-n

Cited by 24 publications

(15 citation statements)

References 25 publications

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“…Results of the current study strongly suggest that in these cells IGFBP-3 is specifically associated with the cell membrane. This is consistent with the data of Oh et al (9) showing the presence of specific membrane proteins responsi- (34 -36) and various other bioassays (21,37,38). This was attributed to the reduced ability of IGFBPs present in the conditioned culture media or extracellular fluids to effectively sequester des-(1-3)-IGF-I.…”

Section: Discussionsupporting

confidence: 82%

Membrane-associated Insulin-like Growth Factor-binding Protein-3 Inhibits Insulin-like Growth Factor-I-induced Insulin-like Growth Factor-I Receptor Signaling in Ishikawa Endometrial Cancer Cells

Karas¹,

Danilenko²,

Fishman³

et al. 1997

Journal of Biological Chemistry

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Section: Discussionsupporting

confidence: 82%

Membrane-associated Insulin-like Growth Factor-binding Protein-3 Inhibits Insulin-like Growth Factor-I-induced Insulin-like Growth Factor-I Receptor Signaling in Ishikawa Endometrial Cancer Cells

Karas¹,

Danilenko²,

Fishman³

et al. 1997

Journal of Biological Chemistry

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“…In a previous study, we have reported a similar IGFBP pattern in conditioned media from primary cultured rat articular chondrocytes (12). Different patterns of IGFBP expression, even within the same species, have been reported in primary cultured chondrocytes (13,38). We attribute this inconsistency to the fact that primary cultured chondrocytes undergo dedifferentiation, with loss of typical chondrocyte markers and, furthermore, that cells are represented by variable, from culture to culture, heterogeneous populations.…”

Section: Igfbp-3 Effect On Chondrogenesismentioning

confidence: 70%

“…Despite these limitations, receptors for IGFs and GH have been identified in chondrocytes (7)(8)(9)(10)(11). Some studies have reported that, in primary cultures of articular chondrocytes, IGFBP-5 is the major IGFBP (12), whereas others have reported that IGFBP-2 is the most abundant IGFBP in cultured chondrocytes (13).…”

mentioning

confidence: 99%

Antiproliferative Effects of Insulin-like Growth Factor-binding Protein-3 in Mesenchymal Chondrogenic Cell Line RCJ3.1C5.18

Spagnoli

Hwa

Horton

et al. 2001

Journal of Biological Chemistry

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Chondrogenesis results from a complex equilibrium between chondrocyte proliferation and differentiation. Insulin-like growth factors (IGFs) have a crucial role in chondrogenesis, but their mechanisms of action are not well defined. IGF-binding protein-3 (IGFBP-3) is the major carrier for circulating IGFs in postnatal life, and has been shown to have IGF-independent effects on proliferation of several cancer cell lines. In this study, we have evaluated the IGF-independent and -dependent effects of IGFBP-3 on chondrocyte proliferation and the relationship of these effects with chondrocyte differentiation stage. We used the RCJ3.1C5.18 nontransformed mesenchymal chondrogenic cell line, which, over 2 weeks of culture, progresses through the differentiation pathway exhibited by chondrocytes in the growth plate. We demonstrated that IGFBP-3 inhibited, in a dose-dependent manner (1-30 nM), the proliferation of chondroprogenitors and early differentiated chondrocytes, stimulated by des-(1-3)-IGF-I and longR 3 -IGF-I (IGF-I analogs with reduced affinity for IGFBP-3), and by insulin and IGF-I. In terminally differentiated chondrocytes, IGFBP-3 retained the ability to inhibit cell proliferation stimulated by IGF-I, but had no effect on cell growth stimulated by insulin, or des-(1-3)-IGF-I or longR 3 IGF-I. By monolayer affinity cross-linking, we demonstrated a specific IGFBP-3-associated cell-membrane protein of ϳ20 kDa. We determined that IGFBP-3 has an antiproliferative effect on chondrocytes and, that this effect is related to the differentiation process. In chondroprogenitors and early differentiated chondrocytes, antiproliferative effect of IGFBP-3 is mainly IGF-independent, whereas, following terminal differentiation this effect is IGF-dependent.

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“…They act mainly as autocrine and/or paracrine factors at or close to their sites of synthesis and have different affinities for the IGFs (Jones & Clemmons 1995). Growth plate chondrocytes produce both IGFs and IGFBPs, which are presumed to be important for chondrocyte regulation and hence for longitudinal growth (Price et al 1992, Bhaumick 1993, Sunic et al 1995, Olney & Mougey 1999. Both IGFs and several IGFBPs are regulated by GCs (Dell et al 1999), both in vitro, e.g.…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone-induced growth inhibition of porcine growth plate chondrocytes is accompanied by changes in levels of IGF axis components

Smink

Koedam²,

Koster³

et al. 2002

Journal of Endocrinology

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High (pharmacological) doses of glucocorticoids inhibit the proliferation of growth plate chondrocytes, which leads to one of the side-effects of these steroids, namely suppression of longitudinal growth. Growth inhibition by glucocorticoids is thought to be mediated in part by impaired action of components of the IGF axis, which are important for chondrocyte regulation and hence for longitudinal growth. The aim of the present study was to determine whether glucocorticoid-induced growth retardation involves changes in IGF axis components. Chondrocytes were isolated from epiphyseal growth plates of neonatal piglets and treated with pharmacological doses of dexamethasone (DXM) for 24 h to study glucocorticoid-induced growth retardation. Under IGF-Isupplemented (10 nM) culture conditions, IGF-binding proteins (IGFBPs)-2, -4 and -5 were secreted by the growth plate chondrocytes and IGFBP-2 protein and mRNA levels were decreased by the DXM treatment, whereas IGFBP-4 and -5 were not affected. Proliferation of the chondrocytes, as measured by [3 H]thymidine incorporation, was 3·5-fold higher in serum-supplemented medium in contrast to IGF-I-supplemented (10 nM) medium. In the presence of serum, DNA synthesis was significantly inhibited by 50-63% when treated with 100 nM DXM, which was prevented by the glucocorticoid-receptor antagonist Org34116. mRNA levels of IGF axis components were determined using Northern blot analysis. IGFBP-2 to -6 were expressed in the chondrocytes, IGFBP-1 was absent and both IGF-I and IGF-II, and the type I and type II IGF receptors were expressed. Treatment with DXM (100 nM) resulted in a 2-fold increase in mRNA levels of both IGFBP-5 and the type I IGF receptor, whereas IGFBP-2 mRNA levels decreased by 55%, in concert with the decrease in protein level observed under IGF-I-supplemented culture conditions. The changes in mRNA levels due to the DXM treatment were prevented by the glucocorticoid receptor antagonist.Our data show that exposure to pharmacological doses of DXM results in inhibition of proliferation and changes in components of the IGF axis, IGFBP-2 and -5 and the type I IGF receptor, suggesting a role for these components in glucocorticoid-induced growth retardation at the local level of the growth plate.

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Insulin-like growth factor binding proteins (IGF-BPs) in bovine articular and ovine growth-plate chondrocyte cultures: their regulation by IGFs and modulation of proteoglycan synthesis

Cited by 24 publications

References 25 publications

Membrane-associated Insulin-like Growth Factor-binding Protein-3 Inhibits Insulin-like Growth Factor-I-induced Insulin-like Growth Factor-I Receptor Signaling in Ishikawa Endometrial Cancer Cells

Membrane-associated Insulin-like Growth Factor-binding Protein-3 Inhibits Insulin-like Growth Factor-I-induced Insulin-like Growth Factor-I Receptor Signaling in Ishikawa Endometrial Cancer Cells

Antiproliferative Effects of Insulin-like Growth Factor-binding Protein-3 in Mesenchymal Chondrogenic Cell Line RCJ3.1C5.18

Dexamethasone-induced growth inhibition of porcine growth plate chondrocytes is accompanied by changes in levels of IGF axis components

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