tailieunhanh - Báo cáo y học: "Pharmacological disruption of insulin-like growth factor 1 binding to IGF-binding proteins restores anabolic responses in human osteoarthritic chondrocytes"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: Pharmacological disruption of insulin-like growth factor 1 binding to IGF-binding proteins restores anabolic responses in human osteoarthritic chondrocytes. | Available online http content 6 5 R393 Research article 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 Open Access Service de Rhumatologie Institut de Recherches Servier Suresnes France 2Orthopédie B Hôpital Cochin Paris France 3Service de Prospective et valorisation scientifique Institut de Recherches Servier Suresnes France Corresponding author Frédéric De Ceuninck 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 ar1 201 2004 De Ceuninck et al. licensee BioMed Central Ltd. This is an Open Access article verbatim copying and redistribution of this article are permitted in all media for any purpose provided this notice is preserved along with the article s original URL. Abstract Insulin-like growth factor 1 IGF-1 has poor anabolic efficacy in 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 synthesis of proteoglycans in cetylpyridinium-chloride-precipitable fractions of cell-associated and secreted 35S-labeled macromolecules. The penetration of NBI-31772 into cartilage was measured by its ability to displace 125I-labeled IGF-1 from cartilage IGFBPs. We found that