Mitochondrial respiratory activity is altered in osteoarthritic human articular chondrocytes.
OBJECTIVE
Osteoarthritis (OA) is a degenerative rheumatic disease that is associated with extracellular matrix degradation and chondrocyte apoptosis in the articular cartilage. The role of mitochondria in degenerative diseases is widely recognized. We undertook this study to evaluate mitochondrial function in normal and OA chondrocytes and to examine age-related changes in mitochondria.


METHODS
Mitochondrial function was evaluated by analyzing respiratory chain enzyme complexes and citrate synthase (CS) activities as well as changes in mitochondrial membrane potential (Delta Psi m). The activities of mitochondrial respiratory chain complexes (complex I: rotenone-sensitive NADH-coenzyme Q(1) reductase; complex II: succinate dehydrogenase; complex III: antimycin-sensitive ubiquinol cytochrome c reductase; and complex IV: cytochrome c oxidase) and CS were measured in human articular chondrocytes isolated from OA and normal cartilage. Delta Psi m was measured by JC-1 using flow cytometry. Statistical analysis was performed using the Mann-Whitney U test and Student's t-test as well as several models of multiple linear regression.


RESULTS
OA articular chondrocytes had reduced activities of complexes II and III compared with cells from normal cartilage. However, the mitochondrial mass was increased in OA. Cultures of OA chondrocytes contained a higher proportion of cells with de-energized mitochondria. We found no relationship between mitochondrial function and donor age either in normal or in OA chondrocytes.


CONCLUSIONS
These findings suggest the involvement of mitochondrial function in the pathophysiology of OA. Cartilage degradation by OA and cartilage aging may be two different processes.
Maneiro
Emilia
E
CHU Juan Canalejo, Coruña, Spain.
Martín
Miguel A
MA
de Andres
María C
MC
López-Armada
Maria J
MJ
Fernández-Sueiro
José L
JL
del Hoyo
Pilar
P
Galdo
Fausto
F
Arenas
Joaquin
J
Blanco
Francisco J
FJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002358:Cartilage, Articular / Q000201:enzymology* / Q000473:pathology; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology; D019902:Chondrocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007425:Intracellular Membranes / Q000502:physiology; D007719:Knee Joint; D008564:Membrane Potentials; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology*; D020370:Osteoarthritis, Knee / Q000201:enzymology* / Q000503:physiopathology
D004791:Enzyme Inhibitors