title: Effects of interleukin-1 and lipopolysaccharides on protein and carbohydrate metabolism in bovine articular cartilage organ cultures.
abstract: The long term (18 day) metabolic response of bovine articular cartilage to treatment with either E. Coli lipopolysaccharide (LPS) or interleukin 1 was studied. For LPS treatment, incorporation of [35S]sulfate into the large proteoglycan population was inhibited 80% while that into the small interstitial proteoglycans was only inhibited 40%. Incorporation of [3H]serine into the large proteoglycan population was inhibited approximately 72% while incorporation into other protein was inhibited only 16%. Furthermore, the rate of catabolism of [3H]serine labeled proteoglycans was increased 2-fold by LPS treatment while the rate of 3H-labeled general protein catabolism was not affected. Incorporation of [3H]glucosamine into hyaluronate was increased; however a correction for changes in the specific activity of the intracellular [3H]glucosamine precursor pool in LPS-treated cultures indicated that the net amount of hyaluronate synthesized was not altered by LPS treatment. The 3H/35S ratios in isolated chondroitin sulfate disaccharides labeled with [35S]sulfate and [3H]glucosamine precursors were significantly changed during long term LPS treatment, suggesting that general carbohydrate pathways are altered. The 3H/35S changes were larger in the disaccharides isolated from the small proteoglycans indicating that different precursor pools, probably in different cell populations, preferentially synthesize this proteoglycan population. Interleukin-1 affected the same chondrocytic pathways as LPS as shown by a) the extent of inhibition of proteoglycan synthesis, b) the selective inhibition of synthesis of the large proteoglycan species, c) acceleration of proteoglycan catabolism, d) net depletion of proteoglycans from the tissue, e) increases in guanidine HCl extractable [3H]hyaluronate, f) increases in levels of prostaglandin E2 synthesis, g) changes in 3H/35S ratios in glycosaminoglycan chains and, h) minimal effects on general protein synthesis.
authors.affiliation: Bone Research Branch, National Institute of Dental Research, Bethesda, Maryland 20892.
authors.forename: T I
authors.initials: TI
authors.lastname: Morales
authors.forename: V C
authors.initials: VC
authors.lastname: Hascall
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D002807:Chondroitin; D002809:Chondroitin Sulfates / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis; D006025:Glycosaminoglycans / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000096:biosynthesis; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D046911:Macromolecular Substances; D009924:Organ Culture Techniques; D011509:Proteoglycans / Q000378:metabolism*
chemical_list: D006025:Glycosaminoglycans; D007375:Interleukin-1; D008070:Lipopolysaccharides; D046911:Macromolecular Substances; D011509:Proteoglycans; D006820:Hyaluronic Acid; D002807:Chondroitin; D002809:Chondroitin Sulfates; D015232:Dinoprostone