Mitochondrial function is altered in articular chondrocytes of an endemic osteoarthritis, Kashin-Beck disease.
OBJECTIVE
Kashin-Beck disease (KBD) is an endemic degenerative osteoarthritis (OA) associated with extracellular matrix degradation and chondrocyte necrosis in the articular and growth plate cartilage. The role of mitochondria in degenerative diseases is widely recognized but its function in KBD is unknown. The aim of this investigation was to evaluate mitochondrial function to understand the mitochondria-mediated caspase activation and apoptosis in adult KBD chondrocytes.


METHODS
Mitochondrial function was evaluated by analyzing the activities of respiratory chain enzyme complexes and citrate synthase (CS), intracellular adenosine triphosphate (ATP) contents, as well as changes in mitochondrial membrane potential (DeltaPsim). Apoptotic cell death was evaluated by analyzing the cytochrome c release from mitochondria to the cytosol, caspase-9 and 3 activities, and the apoptosis rate of KBD articular chondrocytes.


RESULTS
Activities of complexes II, III, IV and V were reduced in KBD articular chondrocytes compared with cells from normal controls. However, the mitochondrial mass was increased in KBD samples. Cultured KBD chondrocytes had a reduction of cellular ATP levels and contained a higher proportion of cells with de-energized mitochondria. Mitochondrial cytochrome c release and activation of caspase-9 and 3 were also observed. The percentages of positive apoptotic chondrocytes from the KBD patient group stained by Hoechst nuclear stain and Annexin V/PI for flow cytometry exhibited higher levels than that of the healthy controls.


CONCLUSIONS
These findings suggest the involvement of mitochondrial function and apoptotic cell death in the pathophysiology of KBD. The dysfunction of the mitochondria may play an important role in KBD articular chondrocytes apoptosis.
Liu
J T
JT
Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
Guo
X
X
Ma
W J
WJ
Zhang
Y G
YG
Xu
P
P
Yao
J F
JF
Bai
Y D
YD
D017209:Apoptosis / Q000502:physiology; D002358:Cartilage, Articular / Q000166:cytology / Q000201:enzymology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000201:enzymology*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D042967:Electron Transport Complex I / Q000378:metabolism; D042963:Electron Transport Complex II / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology* / Q000502:physiology / Q000648:ultrastructure; D020370:Osteoarthritis, Knee / Q000201:enzymology* / Q000503:physiopathology
D003574:Cytochrome c Group; C478189:respiratory complex II; D042963:Electron Transport Complex II; D002950:Citrate (si)-Synthase; D053148:Caspase 3; D053453:Caspase 9; D042967:Electron Transport Complex I