Pharmacological disruption of insulin-like growth factor 1 binding to IGF-binding proteins restores anabolic responses in human osteoarthritic chondrocytes 英文参考文献.docVIP

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Pharmacological disruption of insulin-like growth factor 1 binding to IGF-binding proteins restores anabolic responses in human osteoarthritic chondrocytes 英文参考文献.doc

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Pharmacological disruption of insulin-like growth factor 1 binding to IGF-binding proteins restores anabolic responses in human osteoarthritic chondrocytes 英文参考文献

Available online /content/6/5/R393 Research article Open Access Vol 6 No 5 Pharmacological disruption of insulin-like growth factor 1 binding to IGF-binding proteins restores anabolic responses in human osteoarthritic chondrocytes Frédéric De Ceuninck1, Audrey Caliez1, Laurent Dassencourt1, Philippe Anract2 and Pierre Renard3 1Service de Rhumatologie, Institut de Recherches Servier, Suresnes, France 2Orthopédie B, H?pital Cochin, Paris, France 3Service de Prospective et valorisation scientifique, Institut de Recherches Servier, Suresnes, France Corresponding author: Frédéric De Ceuninck, frederic.deceuninck@ Received: 22 Mar 2004 Revisions requested: 28 Apr 2004 Revisions received: 5 May 2004 Accepted: 19 May 2004 Published: 28 Jun 2004 Arthritis Res Ther 2004, 6:R393-R403 (DOI 10.1186/ar1201) /content/6/5/R393 ? 2004 De Ceuninck et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are per- mitted in all media for any purpose, provided this notice is preserved along with the articles original URL. Abstract Insulin-like growth factor 1 (IGF-1) has poor anabolic efficacy in IGF-1 from cartilage IGFBPs. We found that IGFBP-3 was the major IGFBP secreted by OA cartilage explants and cultured chondrocytes. NBI-31772 inhibited the binding of 125I-labeled cartilage in osteoarthritis (OA), partly because of its sequestration by abnormally high levels of extracellular IGF- binding proteins (IGFBPs). We studied the effect of NBI-31772, a small molecule that inhibits the binding of IGF-1 to IGFBPs, on the restoration of proteoglycan synthesis by human OA chondrocytes. IGFBPs secreted by human OA cartilage or cultured chondrocytes were analyzed by western ligand blot. The ability of NBI-31772 to displace IGF-1 from IGFBPs was measured by radiobinding assay. Anabolic responses in primary cultured chondrocytes were assessed by measuring the IGF-1 to IGF