Musculoskeletal changes following non-invasive knee injury using a novel mouse model of post-traumatic osteoarthritis

Osteoarthritis Cartilage. 2012 Jul;20(7):773-82. doi: 10.1016/j.joca.2012.04.014. Epub 2012 Apr 21.


Objective: Post-traumatic osteoarthritis (PTOA) is a common consequence of traumatic joint injury, with 50% of anterior cruciate ligament (ACL) rupture patients developing PTOA within 10-20 years. Currently accepted mouse models of PTOA initiate symptoms using various methods, none of which faithfully mimic clinically-relevant injury conditions. In this study we characterize a novel non-invasive mouse model of PTOA that injures the ACL with a single load of tibial compression overload. We utilize this model to determine the time course of articular cartilage and subchondral bone changes following knee injury.

Design: Mice were euthanized 1, 3, 7, 14, 28, or 56 days after non-invasive knee injury. Knees were scanned using micro-computed tomography (μCT) in order to quantify subchondral trabecular bone, subchondral bone plate, and non-native bone formation (heterotopic ossification). Development of osteoarthritis (OA) was graded using the osteoarthritis research society international (OARSI) scale on histological sections of injured and uninjured knees.

Results: Following injury we observed a rapid loss of trabecular bone in injured knees compared to uninjured knees by 7 days post-injury, followed by a partial recovery of trabecular bone to a new steady state by 28 days post-injury. We also observed considerable non-native bone formation by 56 days post-injury. Grading of histological sections revealed deterioration of articular cartilage by 56 days post-injury, consistent with development of mild OA.

Conclusions: This study establishes a novel mouse model of PTOA, and describes the time course of musculoskeletal changes following knee injury, helping to establish the window of opportunity for preventative treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anterior Cruciate Ligament Injuries
  • Arthritis, Experimental / diagnostic imaging
  • Arthritis, Experimental / etiology*
  • Arthritis, Experimental / pathology
  • Biomarkers / blood
  • Bone Remodeling / physiology
  • Bone Resorption / diagnostic imaging
  • Bone Resorption / etiology
  • Cartilage, Articular / pathology
  • Disease Progression
  • Extracellular Matrix Proteins / blood
  • Glycoproteins / blood
  • Knee Injuries / complications*
  • Knee Injuries / diagnostic imaging
  • Knee Injuries / pathology
  • Male
  • Matrilin Proteins
  • Mice
  • Mice, Inbred C57BL
  • Ossification, Heterotopic / diagnostic imaging
  • Ossification, Heterotopic / etiology
  • Osteoarthritis / diagnostic imaging
  • Osteoarthritis / etiology*
  • Osteoarthritis / pathology
  • Rupture / complications
  • Rupture / diagnostic imaging
  • Rupture / pathology
  • Stress, Mechanical
  • X-Ray Microtomography


  • Biomarkers
  • Extracellular Matrix Proteins
  • Glycoproteins
  • Matn1 protein, mouse
  • Matrilin Proteins