title: The role of mitochondria in osteoarthritis.
abstract: Mitochondria are important regulators of cellular function and survival that may have a key role in aging-related diseases. Mitochondrial DNA (mtDNA) mutations and oxidative stresses are known to contribute to aging-related changes. Osteoarthritis (OA) is an aging-associated rheumatic disease characterized by articular cartilage degradation and elevated chondrocyte mortality. Articular cartilage chondrocytes survive and maintain tissue integrity in an avascular, low-oxygen environment. Recent ex vivo studies have reported mitochondrial dysfunction in human OA chondrocytes, and analyses of mitochondrial electron transport chain activity in these cells show decreased activity of Complexes I, II and III compared to normal chondrocytes. This mitochondrial dysfunction may affect several pathways that have been implicated in cartilage degradation, including oxidative stress, defective chondrocyte biosynthesis and growth responses, increased cytokine-induced chondrocyte inflammation and matrix catabolism, cartilage matrix calcification, and increased chondrocyte apoptosis. Mitochondrial dysfunction in OA chondrocytes may derive from somatic mutations in the mtDNA or from the direct effects of proinflammatory mediators such as cytokines, prostaglandins, reactive oxygen species and nitric oxide. Polymorphisms in mtDNA may become useful as biomarkers for the diagnosis and prognosis of OA, and modulation of serum biomarkers by mtDNA haplogroups supports the concept that mtDNA haplogroups may define specific OA phenotypes in the complex OA process.
authors.affiliation: Osteoarticular and Aging Research Laboratory, Biomedical Research Center, Rheumatology Division, INIBIC-Hospital Universitario A Coruña, Xubias de Arriba 84, A Coruña, Spain. fblagar@sergas.es
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Blanco
authors.forename: Ignacio
authors.initials: I
authors.lastname: Rego
authors.forename: Cristina
authors.initials: C
authors.lastname: Ruiz-Romero
mesh_terms: D019902:Chondrocytes / Q000473:pathology / Q000502:physiology; D004272:DNA, Mitochondrial / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D010003:Osteoarthritis / Q000473:pathology / Q000503:physiopathology*
chemical_list: D004272:DNA, Mitochondrial