title: Beneficial effect of a sturgeon-based bioactive compound on gene expression of tumor necrosis factor-alpha, matrix metalloproteinases and type-10 collagen in human chondrocytes.
abstract: In the present study, we examined the effect of a marine bioactive compound containing high-purity caviar-derived DNA, collagen elastin and protein extracts from sturgeon (LD-1227, Caviarlieri, Laboratoires Dom, Switzerland) on IL-1beta-induced activation and production of TNFalpha and MMP-13 in human osteo-arthritis (OA) chondrocytes and intracellular signaling factors. Human chondrocytes were derived from OA cartilage and stimulated with IL-1beta. Gene expression of TNFalpha, MMP-13, MMP-1 and Col10A1 was measured by quantitative RT-PCR. TNFalpha protein in culture medium was determined using cytokine-specific ELISA. Western immunoblotting was used to analyze the MMP-13 production in the culture medium and the activation of NF-kB. DNA binding activity of NF-kB p65 was determined using a highly sensitive and specific ELISA. MMP-13 activity in the culture medium was assayed by gelatine zymography. LD-1227 significantly decreased IL-1beta-stimulated gene expression and production of TNFalpha, MMP-1, MMP-13 and Col10A1 in human chondrocytes. The inhibitory effect of LD-1227 on the IL-1beta-induced expression of these genes was mediated at least in part via suppression of NF-kB p65. These data show that LD-1227 can inhibit IL-1beta-induced proliferation and inflammatory reactions via inhibited activation of the transcription factor NF-kB pathway in human chondrocytes derived from OA patients. These novel pharmacological actions of LD-1227 on IL-1beta-stimulated human OA chondrocytes provide suggestions that this marine biology compound may inhibit cartilage degradation by suppressing IL-1beta-mediated activation and the catabolic response in human chondrocytes.
authors.affiliation: Dept of Internal Medicine, University of Catania, Catania, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Catanzaro
authors.forename: F
authors.initials: F
authors.lastname: Marotta
authors.forename: S
authors.initials: S
authors.lastname: Jain
authors.forename: R
authors.initials: R
authors.lastname: Rastmanesh
authors.forename: F
authors.initials: F
authors.lastname: Allegri
authors.forename: G
authors.initials: G
authors.lastname: Celep
authors.forename: A
authors.initials: A
authors.lastname: Lorenzetti
authors.forename: A
authors.initials: A
authors.lastname: Polimeni
authors.forename: H
authors.initials: H
authors.lastname: Yadav
mesh_terms: D000368:Aged; D000818:Animals; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D024121:Collagen Type X / Q000096:biosynthesis*; D045424:Complex Mixtures / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D029941:Fish Proteins / Q000737:chemistry / Q000494:pharmacology*; D005399:Fishes; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis*; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis*; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D024121:Collagen Type X; D045424:Complex Mixtures; D029941:Fish Proteins; C508585:IL1B protein, human; D053583:Interleukin-1beta; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1