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Early detection of aging cartilage and osteoarthritis in mice and patient samples using atomic force microscopy

Nature Nanotechnology volume 4, pages 186–192 (2009)Cite this article

A Corrigendum to this article was published on 04 November 2010

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Abstract

The pathological changes in osteoarthritis—a degenerative joint disease prevalent among older people—start at the molecular scale and spread to the higher levels of the architecture of articular cartilage to cause progressive and irreversible structural and functional damage. At present, there are no treatments to cure or attenuate the degradation of cartilage. Early detection and the ability to monitor the progression of osteoarthritis are therefore important for developing effective therapies. Here, we show that indentation-type atomic force microscopy can monitor age-related morphological and biomechanical changes in the hips of normal and osteoarthritic mice. Early damage in the cartilage of osteoarthritic patients undergoing hip or knee replacements could similarly be detected using this method. Changes due to aging and osteoarthritis are clearly depicted at the nanometre scale well before morphological changes can be observed using current diagnostic methods. Indentation-type atomic force microscopy may potentially be developed into a minimally invasive arthroscopic tool to diagnose the early onset of osteoarthritis in situ.

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Figure 1: Surface imaging and indentation tests for articular cartilage of normal mice at various ages.
Figure 2: Surface imaging and indentation tests for articular cartilage of wild-type control and Col9a1−/− knockout mice at 1 month of age.
Figure 3: Statistical analyses of articular cartilage properties assessed by AFM from wild-type control and Col9a1−/− knockout mice at various ages.
Figure 4: Assessing osteoarthritis in human patients.

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Change history

  • 04 November 2010

    In the version of this Article originally published, a systematic error affected all the values of microstiffness presented in the paper (including in the figures and figure captions). This error resulted in all the values of microstiffness being too high by a factor of √π. The values for nanostiffness are not affected and this error does not affect the conclusions of the paper. This error has now been corrected in the HTML and PDF versions of the text. The Supplementary Information and corresponding e-mail address have also been updated.

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Acknowledgements

This work was supported by an NCCR program grant on ‘Nanoscale Science’ awarded by the Swiss National Science Foundation, the M. E. Müller Foundation of Switzerland, the Canton Basel-Stadt, and the Max Planck Society. Part of the work has also been supported by the Hardy and Otto Frey-Zünd Foundation, ProMotio Foundation for Biomechanical Research and other private promoters supporting the efforts of the University of Basel Laboratory for Orthopedic Biomechanics. Moreover, we thank Nanoworld AG (L. Aeschimann, M. Burri) for the silicon AFM probes and for the SEM image of the microspherical tip, and Z. Farkas for technical assistance. The authors thank F. Wolf for some of the glycosaminoglycan/DNA analysis. We thank T. Staehelin for critical review of the manuscript and discussion of the data, and Z. Housley for proofreading the manuscript.

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Authors and Affiliations

  1. M.E. Müller Institute for Structural Biology, Biozentrum University of Basel, Switzerland

    Martin Stolz, Werner Baschong & Ueli Aebi

  2. Department of Biophysical and Electronic Engineering, University of Genoa, Italy

    Riccardo Gottardi & Roberto Raiteri

  3. Departments of Surgery and of Biomedicine, University Hospital Basel, Switzerland

    Sylvie Miot & Ivan Martin

  4. Institute of Microtechnology, University of Neuchâtel, Switzerland

    Raphaël Imer & Urs Staufer

  5. Micro and Nano Engineering Lab, TU Delft, The Netherlands

    Urs Staufer

  6. Max Planck Institute of Biochemistry, Martinsried, Germany

    Aurelia Raducanu & Attila Aszodi

  7. Center for Microscopy, University of Basel, Switzerland

    Marcel Düggelin

  8. Department of Oral Surgery, Oral Radiology and Oral Medicine, University of Basel, Switzerland

    Werner Baschong

  9. Laboratory for Orthopaedic Biomechanics, University of Basel Faculty of Medicine, Basel, Switzerland

    A. U. Daniels

  10. Department of Orthopaedic Surgery and Traumatology, Kantonsspital Bruderholz/Basel, Switzerland

    Niklaus F. Friederich

Authors
  1. Martin Stolz
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  14. Ueli Aebi
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Contributions

M.S., W.B., A.A. and U.A. conceived and designed the experiments. R.R. developed the software for analysing force maps. R.I. and U.S. developed and produced the microfabricated spherical tips. N.F. provided all issues related to clinics. M.S., R.G., S.M., A.R., M.D. and A.A. performed the experiments. M.S., I.M., A.D., A.A. and U.A. co-wrote the paper. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Martin Stolz.

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Stolz, M., Gottardi, R., Raiteri, R. et al. Early detection of aging cartilage and osteoarthritis in mice and patient samples using atomic force microscopy. Nature Nanotech 4, 186–192 (2009). https://doi.org/10.1038/nnano.2008.410

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