title: Osteonectin/SPARC is a product of articular chondrocytes/cartilage and is regulated by cytokines and growth factors.
abstract: Rabbit articular chondrocytes maintained in monolayer, synthesized and secreted a 46 kDa protein into the culture medium. N-terminal sequence analysis and immunoprecipitation of the radiolabeled material revealed this protein to be osteonectin (ON)/SPARC, a protein previously shown to be present in bone. When chondrocytes were exposed to interleukin-1, a cytokine with matrix degradative properties, ON synthesis and secretion was greatly inhibited. However, this was specific to IL-1 since two other pro-inflammatory cytokines (tumor-necrosis factor-alpha and interleukin-6) with properties similar to IL-1, failed to cause any discernible effect on ON synthesis. Several growth factors (TGF-beta, PDGF, and IGF-1), that have been shown to stimulate other cartilage matrix macromolecular synthesis, also stimulated ON synthesis and were also able to reverse the inhibitory effect of IL-1 on ON synthesis. These observations were also demonstrated in explant cultures of cartilage. Our studies suggest that ON is a biosynthetic product of articular cartilage and could play a role in cartilage structure and/or function.
authors.affiliation: Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285.
authors.forename: S
authors.initials: S
authors.lastname: Chandrasekhar
authors.forename: A K
authors.initials: AK
authors.lastname: Harvey
authors.forename: M G
authors.initials: MG
authors.lastname: Johnson
authors.forename: G W
authors.initials: GW
authors.lastname: Becker
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009924:Organ Culture Techniques; D015676:Osteonectin / Q000096:biosynthesis* / Q000302:isolation & purification; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D021382:Protein Sorting Signals / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D006133:Growth Substances; D007375:Interleukin-1; D015850:Interleukin-6; D015676:Osteonectin; D010982:Platelet-Derived Growth Factor; D021382:Protein Sorting Signals; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I