title: Hypoxia conditions differentially modulate human normal and osteoarthritic chondrocyte proteomes.
abstract: Osteoarthritis (OA) is a degenerative disease characterized by the degradation of articular cartilage. This tissue is avascular, and it is characterized by the low oxygen tension and poor nutrient availability for its cells, the chondrocytes. Hypoxia conditions have been reported to stimulate chondrogenesis and synthesis of extracellular matrix components. Therefore, we aimed to analyze the effect of hypoxia on normal and osteoarthritic cartilage cell cultures by a proteomic approach based in Two-dimensional gel electrophoresis followed by MALDI-TOF/TOF mass spectrometry protein identification. Twenty-eight proteins were found to be modulated by hypoxia in normal chondrocytes and 11 in OA cells when compared to their normoxia controls. In both cases, a hypoxia-dependent decrease in metabolism-related proteins was detected. We also identified 42 protein forms that were altered in OA chondrocytes under hypoxia when compared to normal cells. The upregulation of cyclophylin A (PPIA) and Tumor necrosis factor receptor associated protein 1 (TRAP1) was confirmed both in cultured chondrocytes and in cartilage tissue. Our work shows how hypoxia conditions induce diverse modifications in the proteomic profile of normal and OA human articular chondrocytes, which probably renders a different capacity of OA and normal cells to react under a hypoxic environment.
authors.affiliation: Unidad de Investigación del Envejecimiento Osteoarticular, INIBIC-Complejo Hospitalario Universitario A Coruña, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ruiz-Romero
authors.forename: Valentina
authors.initials: V
authors.lastname: Calamia
authors.forename: Beatriz
authors.initials: B
authors.lastname: Rocha
authors.forename: Jesús
authors.initials: J
authors.lastname: Mateos
authors.forename: Patricia
authors.initials: P
authors.lastname: Fernández-Puente
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Blanco
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002358:Cartilage, Articular; D016022:Case-Control Studies; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D021984:Cyclophilin A / Q000737:chemistry / Q000378:metabolism; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D020543:Proteome / Q000737:chemistry / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D018709:Statistics, Nonparametric; D014357:Trypsin / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C497442:HIF1A protein, human; D018841:HSP90 Heat-Shock Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010446:Peptide Fragments; D011506:Proteins; D020543:Proteome; C092306:TRAP1 protein, human; D014357:Trypsin; D021984:Cyclophilin A