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Mechanisms of Disease: role of chondrocytes in the pathogenesis of osteoarthritis—structure, chaos and senescence

Nature Clinical Practice Rheumatology volume 3, pages 391–399 (2007)Cite this article

Abstract

The extracellular matrix of articular cartilage is the primary target of osteoarthritic cartilage degradation. However, cartilage cells have a pivotal role during osteoarthritis, as they are mainly responsible for the anabolic–catabolic balance required for matrix maintenance and tissue function. In addition to the severe changes in the extracellular matrix, the cells also display abnormalities during osteoarthritic cartilage degeneration, such as inappropriate activation of anabolic and catabolic activities, and alterations in cell number through processes like proliferation and (apoptotic) cell death. The cells are exposed to additional stimuli such as nonphysiologic loading conditions and byproducts of matrix destruction, as well as abnormal levels of cytokines and growth factors. This exposure can lead to a structured cellular response pattern that may be either beneficial or detrimental to the cartilage tissue. Potentially even more problematic for preserving tissue homeostasis, neighboring osteoarthritic chondrocytes display strong heterogeneity in their phenotype, gene expression patterns, and cellular responses. As the disease progresses, osteoarthritic chondrocytes can no longer maintain tissue integrity. Evidence suggests that cell aging is important in the pathogenesis of osteoarthritis. Thus, anti-aging strategies might complement existing therapeutic targets related to anabolism, catabolism, inflammation, and apoptosis—processes that are integral to the pathogenesis of osteoarthritis.

Key Points

  • Osteoarthritic chondrocytes are exposed to many external factors and respond with a large spectrum of phenotypic and behavioral changes (anabolic, catabolic, proliferative, apoptotic, etc.)

  • Many of the biological changes occurring in osteoarthritic chondrocytes mimic the differentiation pattern that occurs during fetal skeletogenesis

  • The extraordinarily pleomorphic behavior of osteoarthritic chondrocytes suggests an unstructured/stochastic reaction pattern

  • Damage to the genome induced by oxidative damage and/or reactive oxygen species may be responsible for some of the so far unexplained heterogenous gene transcription patterns

  • Premature aging of chondrocytes might be important in the pathogenesis of OA

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Figure 1: Cell biology of osteoarthritis: how do chondrocytes react?
Figure 2: The developmental model of chondrocyte behavior applied to osteoarthritis in the adult
Figure 3: Chondrocyte behavior: structured and unstructured
Figure 4: Osteoarthritic chondrocytes are not apoptotic, but degenerated and deranged

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Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft (DFG Ai 20/7–1).

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Authors and Affiliations

  1. J Haag is a Senior Research Fellow and PM Gebhard is a PhD Student. A McAlinden is an Assistant Professor in the Department of Orthopedic Surgery, T Aigner is a Senior Staff Pathologist and Deputy Director of the Institute of Pathology, University of Leipzig, Germany, where S Söder is a Clinical Research Fellow, Washington University School of Medicine, St Louis, MO, USA.,

    Thomas Aigner, Stefan Söder, Pia M Gebhard, Audrey McAlinden & Jochen Haag

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Correspondence to Thomas Aigner.

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Aigner, T., Söder, S., Gebhard, P. et al. Mechanisms of Disease: role of chondrocytes in the pathogenesis of osteoarthritis—structure, chaos and senescence. Nat Rev Rheumatol 3, 391–399 (2007). https://doi.org/10.1038/ncprheum0534

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