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Mouse Genetics pp 401–419Cite as

Experimental Osteoarthritis Models in Mice

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1194))

Abstract

Osteoarthritis (OA) is a slowly progressing, degenerative disorder of synovial joints culminating in the irreversible destruction of articular cartilage and subchondral bone. It affects almost everyone over the age of 65 and influences life quality of affected individuals with enormous costs to the health care system. Current therapeutic strategies seek to ameliorate pain and increase mobility; however, to date none of them halts disease progression or regenerates damaged cartilage or bone. Thus, there is an ultimate need for the development of new, noninvasive treatments that could substitute joint replacement for late- or end-stage patients. Therefore, osteoarthritis animal models for mimicking of all OA features are important. Mice develop an OA pathology that is comparable to humans, rapidly develop OA due to the short lifetime and show reproducible OA symptoms. They provide a versatile and widely used animal model for analyzing molecular mechanisms of OA pathology. One major advantage over large animal models is the availability of knockout or transgenic mice strains to examine genetic predispositions/contributions to OA.

In this chapter, we describe three widely used instability-inducing murine osteoarthritis models. The most common two methods for surgical induction are: (1) destabilization of the medial meniscus (DMM) and (2) anterior cruciate ligament transection (ACLT). In the DMM model, the medial meniscotibial ligament is transected while in the ACLT model the anterior cruciate ligament is destroyed. In the third, chemical induced instability method, intraarticular collagenase is injected into the knee joint. Intraarticular collagenase weakens articular ligaments which cause instability of the joint, and full-blown OA develops within 6 weeks. For morphological evaluation, we correspond mainly to the recommendations of OARSI for histological assessment of osteoarthritis in mouse. For statistical evaluation summed or mean scores of all four knee areas (medial tibial plateau (MTP), medial tibial condyle (MFC), lateral tibial plateau (LTP) or lateral femoral condyle (LFC)), medial and/or lateral regions are used.

In future, not only large animal models like guinea pigs, sheep, goats, or horses will be important for a better understanding of osteoarthritis, but especially the mouse model with its rapid development of osteoarthritis and its numerous advantages by providing knockout or transgenic strains will become more and more relevant for drug development and determination of genetic predispositions of osteoarthritis pathology.

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Acknowledgements

This work was supported by the DFG grant GR1301/9-1 assigned to SG.

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Authors and Affiliations

  1. Orthopaedic Surgery, Experimental Orthopaedics, Centre for Medical Biotechnology, BioPark I, University of Regensburg, Regensburg, Germany

    Julia Lorenz & Susanne Grässel Ph.D.

  2. Department of Orthopaedics, University of Regensburg, ZMB/BioPark 1, Josef-Engert-Str. 9, 93053, Regensburg, Germany

    Susanne Grässel Ph.D.

Authors
  1. Julia Lorenz
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  2. Susanne Grässel Ph.D.
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Corresponding author

Correspondence to Susanne Grässel Ph.D. .

Editor information

Editors and Affiliations

  1. Stem Cell Regulation and Animal Aging Section, Basic Research Laboratory,, National Cancer Institute, National Institutes of Health, Frederick, MD, USA

    Shree Ram Singh

  2. Genetically Engineered Mouse Modeling Core/Department of Molecular Virology, Immunology and Medical Genetics, Wexner Medical Center, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA

    Vincenzo Coppola

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Lorenz, J., Grässel, S. (2014). Experimental Osteoarthritis Models in Mice. In: Singh, S., Coppola, V. (eds) Mouse Genetics. Methods in Molecular Biology, vol 1194. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1215-5_23

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  • DOI: https://doi.org/10.1007/978-1-4939-1215-5_23

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1214-8

  • Online ISBN: 978-1-4939-1215-5

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