title: Investigation of chondrocyte hypertrophy and cartilage calcification in a full-depth articular cartilage explants model.
abstract: Articular cartilage deterioration, which includes cartilage degradation and chondrocyte hypertrophy, is a hallmark of degenerative joint diseases (DJD). Chondrocyte hypertrophy is initiated in the deep layer of the cartilage; thus, a robust explants model for investigation of hypertrophy should include this zone. The aim of this study was to characterize and investigate the hypertrophy-promoting potential of different endogenous factors on an ex vivo articular cartilage model. The full-depth cartilage explants were harvested from bovine femoral condyle and cultured for 13 days in different conditions: 10 ng/ml oncostatin M + 20 ng/ml TNF-α; 100 ng/ml IGF1; 10-100 ng/ml bFGF; 10-100 ng/ml BMP2; 50 μg/ml ascorbic acid in combination with 10 mM β-glycerophosphate; and 20-100 ng/ml triiodothyronine. The cellular activity and morphology, degradation, formation and calcification, and expression level of hypertrophic markers were investigated. The hypertrophic factors tested all induced cellular activity and marked morphological changes starting at day 4, however, not in a synchronized manner. Both cartilage degradation and formation were induced by T3 (P < 0.05). Only T3 had a full hypertrophic gene expression profile (P < 0.05). We developed and characterized a novel model for investigation of chondrocyte hypertrophy. We speculated that this can become an important investigatory tool for investigation of matrix turnover, chondrocyte hypertrophy and cartilage calcification that are associated with DJD pathogenesis.
authors.affiliation: Cartilage Biology and Biomarkers, R&D, Nordic Bioscience A/S, Herlev Hovedgade 207, 2730 Herlev, Denmark. pp@nordicbioscience.com
authors.forename: Pingping
authors.initials: P
authors.lastname: Chen-An
authors.forename: Kim Vietz
authors.initials: KV
authors.lastname: Andreassen
authors.forename: Kim
authors.initials: K
authors.lastname: Henriksen
authors.forename: Morten Asser
authors.initials: MA
authors.lastname: Karsdal
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Bay-Jensen
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D002114:Calcinosis / Q000473:pathology*; D002358:Cartilage, Articular / Q000473:pathology*; D002417:Cattle; D019902:Chondrocytes / Q000473:pathology*; D024121:Collagen Type X / Q000032:analysis; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D020869:Gene Expression Profiling; D006984:Hypertrophy; D007592:Joint Diseases / Q000209:etiology; D053509:Matrix Metalloproteinase 13 / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D055396:Bone Morphogenetic Protein 2; D024121:Collagen Type X; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D000469:Alkaline Phosphatase; D053509:Matrix Metalloproteinase 13