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Closed Joint ACL Disruption Murine Model of PTA

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Post-Traumatic Arthritis

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Abstract

Closed, nonsurgical models of induced mouse OA are becoming more accepted in the field of OA research. These models rely on intra-articular fracture, repeated bouts of mechanical overloading of the joint, or rupture of the anterior cruciate ligament. The ACL rupture model described in this chapter results in immediate mechanical damage to the ACL, either as an avulsion fracture or midsection ACL tear depending on the loading rate. This immediate damage causes joint instability and initiates a biological injury response that includes acute changes in gene expression, increased cytokine production, as well as increased expression of proteinases in the ADAMTS and MMP families. The expression of many anabolic genes also results, indicating a wound-repair response. The initial changes in gene expression are followed by substantial remodeling of subchondral bone during the first 2 weeks, and osteophyte formation at later time points. Serum biomarkers of OA development (COMP) and bone resorption (CTX-I) become elevated. Histological assessment shows markers of OA progression that include synovial hyperplasia and fibrosis, loss of surface lamina and superficial zone chondrocytes, and at later time points significant proteoglycan loss and cartilage degradation. In summary, the closed joint ACL rupture model approximates many of the clinical features of joint injury leading to OA, and holds promise for the study of early intervention strategies to prevent OA initiation after injury.

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Author information

Authors and Affiliations

  1. Department of Orthopedic Surgery, University of California Davis, Research Building 1, Suite 2000, 4635 Second Avenue, Sacramento, CA, USA

    Blaine A. Christiansen Ph.D.

  2. University of California Davis, Research Building 1, Suite 2000, 4635 Second Avenue, Sacramento, CA, USA

    Jasper H. N. Yik Ph.D.

  3. Department of Orthopedic Surgery, University of California Davis, Research Building 1, Room 3004, 4635 Second Avenue, Sacramento, CA, USA

    Dominik R. Haudenschild Ph.D.

Authors
  1. Blaine A. Christiansen Ph.D.
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  2. Jasper H. N. Yik Ph.D.
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  3. Dominik R. Haudenschild Ph.D.
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Corresponding authors

Correspondence to Blaine A. Christiansen Ph.D. or Dominik R. Haudenschild Ph.D. .

Editor information

Editors and Affiliations

  1. Professor, Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina, USA

    Steven A. Olson, MD

  2. Laszlo Ormandy Professor, Department of Orthopedic Surgery, Duke University Medical Center, Durham, North Carolina, USA

    Farshid Guilak, PhD

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Christiansen, B.A., Yik, J.H.N., Haudenschild, D.R. (2015). Closed Joint ACL Disruption Murine Model of PTA. In: Olson, MD, S., Guilak, PhD, F. (eds) Post-Traumatic Arthritis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-7606-2_7

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  • DOI: https://doi.org/10.1007/978-1-4899-7606-2_7

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4899-7605-5

  • Online ISBN: 978-1-4899-7606-2

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