title: Interleukin-1-induced alterations in proteoglycan metabolism and matrix assembly.
abstract: In cartilage, the large chondroitin sulfate proteoglycan exists as aggregates by interacting with link protein and hyaluronic acid. In diseases associated with cartilage degeneration, the proteoglycan does not aggregate because of a defect in the hyaluronate-binding activity. Since interleukin-1 (IL-1) is a secretory product of activated macrophages and may influence the cartilage function in joints, we studied the effects of IL-1 on the synthesis and assembly of proteoglycan by rabbit articular chondrocytes in culture. IL-1-treated cells showed a modest increase in the total proteoglycan synthesis, but also showed a more pronounced decrease in the incorporation of extracellular matrix. Affinity chromatography of the conditioned media on hyaluronic acid-Sepharose revealed that all of the proteoglycan of control cells strongly bound to hyaluronate. The IL-1-treated medium contained two fractions: one that was strongly bound to the column and a second that did not bind. The results demonstrate that the IL-1-treated cells cannot incorporate proteoglycan into the matrix partly because of a defect in the proteoglycan molecules and partly due to other mechanisms regulating proteoglycan assembly.
authors.affiliation: Department of Connective Tissue Research, Lilly Research Laboratories, Indianapolis, Indiana 46285.
authors.forename: S
authors.initials: S
authors.lastname: Chandrasekhar
authors.forename: K
authors.initials: K
authors.lastname: Phadke
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002358:Cartilage, Articular / Q000378:metabolism*; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D003470:Culture Media / Q000032:analysis; D005109:Extracellular Matrix / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages; D011509:Proteoglycans / Q000032:analysis / Q000096:biosynthesis*; D011817:Rabbits
chemical_list: D003470:Culture Media; D007375:Interleukin-1; D011509:Proteoglycans; D006820:Hyaluronic Acid