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The role of mitochondria in osteoarthritis

Nature Reviews Rheumatology volume 7, pages 161–169 (2011)Cite this article

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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.

Key Points

  • Mitochondrial functions, including mitochondrial respiratory chain (MRC) activity and ATP synthesis, are altered in osteoarthritis (OA) chondrocytes

  • Mitochondrial dysfunction may influence several of the specific pathways involved in OA pathology, including oxidative stress, chondrocyte apoptosis, cytokine-induced chondrocyte inflammation and matrix catabolism, and calcification of the cartilage matrix

  • OA chondrocyte mitochondrial dysfunction may originate from somatic mutations in the mitochondrial DNA (mtDNA) or from the direct effects of proinflammatory cytokines, prostaglandins, reactive oxygen species and nitric oxide on the MRC and ATP synthesis

  • mtDNA haplogroups may serve as useful biomarkers for the diagnosis or prognosis of OA, and might define distinct, specific OA phenotypes with different levels of serum OA biomarkers

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Figure 1: Structure and function of mitochondria.
Figure 2: Diffusion of glucose and oxygen into articular cartilage.
Figure 3: SNPs giving rise to mtDNA haplogroups.
Figure 4: Influence of mtDNA haplogroups in OA.

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Acknowledgements

This work was supported by grants from Secretaria I+D+I Xunta Galicia (PGIDIT06PXIC916175PN); Fundación Española de Reumatologia (programa GEN-SER); Instituto de Salud Carlos III (CIBER- CB06/01/0040); Fondo Investigacion Sanitaria-(PI 08/2028); Ministerio Ciencia e Innovacion PLE2009-0144, with participation of FEDER (European Community). Ignacio Rego was supported by Contrato de Apoyo a la Investigación-Fondo Investigación Sanitaria (CA06/01102). Cristina Ruiz-Romero was supported by Programa Miguel Servet, Fondo Investigación Sanitaria-Spain CP09/00114. The authors express their appreciation to Dr Joaquin Arenas and Miguel A. Martin for scientific criticism of their work on the mitochondrion and for their constant support in developing mitochondrial methodologies.

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  1. Rheumatology Division, Osteoarticular and Aging Research Laboratory, Biomedical Research Center, INIBIC-Hospital Universitario A Coruña, Xubias de Arriba 84, A Coruña, 15006, Spain

    Francisco J. Blanco, Ignacio Rego & Cristina Ruiz-Romero

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I. Rego and C. Ruiz-Romero researched data for the article. All authors made substantial contributions to discussion of the content. F. J. Blanco wrote the article. All authors performed review/editing of the manuscript before submission.

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Blanco, F., Rego, I. & Ruiz-Romero, C. The role of mitochondria in osteoarthritis. Nat Rev Rheumatol 7, 161–169 (2011). https://doi.org/10.1038/nrrheum.2010.213

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