Mitochondrial function is altered in articular chondrocytes of an endemic osteoarthritis, Kashin-Beck disease

J. T. Liu, X. Guo, W. J. Ma, Y. G. Zhang, P. Xu, J. F. Yao, Yidong Bai

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

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 (Δ Ψm). 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)1218-1226
Number of pages9
JournalOsteoarthritis and Cartilage
Volume18
Issue number9
DOIs
StatePublished - Sep 2010

Fingerprint

Kashin-Beck Disease
Chondrocytes
Osteoarthritis
Joints
Mitochondria
Cell death
Caspase 9
Apoptosis
Cytochromes c
Caspase 3
Cell Death
Adenosine Triphosphate
Chemical activation
Citrate (si)-Synthase
Proteins
Growth Plate
Mitochondrial Membrane Potential
Annexin A5
Flow cytometry
Caspases

Keywords

  • Apoptosis
  • Chondrocytes
  • Kashin-Beck disease
  • Mitochondria

ASJC Scopus subject areas

  • Biomedical Engineering
  • Orthopedics and Sports Medicine
  • Rheumatology

Cite this

Mitochondrial function is altered in articular chondrocytes of an endemic osteoarthritis, Kashin-Beck disease. / Liu, J. T.; Guo, X.; Ma, W. J.; Zhang, Y. G.; Xu, P.; Yao, J. F.; Bai, Yidong.

In: Osteoarthritis and Cartilage, Vol. 18, No. 9, 09.2010, p. 1218-1226.

Research output: Contribution to journalArticle

Liu, J. T. ; Guo, X. ; Ma, W. J. ; Zhang, Y. G. ; Xu, P. ; Yao, J. F. ; Bai, Yidong. / Mitochondrial function is altered in articular chondrocytes of an endemic osteoarthritis, Kashin-Beck disease. In: Osteoarthritis and Cartilage. 2010 ; Vol. 18, No. 9. pp. 1218-1226.
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AU - Yao, J. F.

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N2 - 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 (Δ Ψm). 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. Conclusion: 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.

AB - 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 (Δ Ψm). 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. Conclusion: 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.

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