title: A novel rat model for subchondral microdamage in acute knee injury: a potential mechanism in post-traumatic osteoarthritis.
abstract: Subchondral microdamage may play an important role in post-traumatic osteoarthritis (PTOA) development following anterior cruciate ligament (ACL) rupture. It remains unknown whether this injury mechanism causes subchondral microdamage, or whether its repair occurs by targeted osteoclast-mediated remodeling. If so these events may represent a mechanism by which subchondral bone is involved in PTOA. Our objective was to test the hypothesis that subchondral microdamage occurs, and is co-localized with remodeling, in a novel rat model of ACL rupture.
  
  
  
  We developed a novel non-invasive rat animal model for ACL rupture and subchondral microdamage generation. By inducing ACL rupture noninvasively rather than surgically, this more closely mimics the clinical injury. MicroCT, MRI and histological methods were used to measure microstructural changes, ligament damage, and cellular/matrix degeneration, respectively.
  
  
  
  We reproducibly generated ACL rupture without damage to other soft joint tissues. Immediately after injury, increased microdamage was found in the postero-medial aspect of the tibia. Microstructural parameters showed increased resorption at 2 weeks, which returned to baseline. Dynamic histomorphometry showed increased calcein label uptake in the same region at 4 and 8 weeks. Chondrocyte death and protease activity in cartilage was also noted, however whether this was directly linked to subchondral changes is not yet known. Similarly, cartilage scoring showed degradation at 4 and 8 weeks post-injury.
  
  
  
  This study shows that our novel model can be used to study subchondral microdamage after ACL-rupture, and its association with localized remodeling. Cartilage degeneration, on a similar time-scale to other models, is also a feature of this system.
authors.affiliation: Department of Orthopaedic Surgery, New York University School of Medicine, New York, NY, USA. Electronic address: Austin.Ramme@med.nyu.edu.
authors.forename: A J
authors.initials: AJ
authors.lastname: Ramme
authors.affiliation: Department of Orthopaedic Surgery, New York University School of Medicine, New York, NY, USA. Electronic address: Matin.Lendhey@nyumc.org.
authors.forename: M
authors.initials: M
authors.lastname: Lendhey
authors.affiliation: Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY, USA. Electronic address: Jose.Raya@nyumc.org.
authors.forename: J G
authors.initials: JG
authors.lastname: Raya
authors.affiliation: Department of Orthopaedic Surgery, New York University School of Medicine, New York, NY, USA. Electronic address: Thorsten.Kirsch@nyumc.org.
authors.forename: T
authors.initials: T
authors.lastname: Kirsch
authors.affiliation: Department of Orthopaedic Surgery, New York University School of Medicine, New York, NY, USA; Department of Mechanical and Aerospace Engineering, New York University Tandon School of Engineering, New York, NY, USA. Electronic address: oran.kennedy@nyumc.org.
authors.forename: O D
authors.initials: OD
authors.lastname: Kennedy
mesh_terms: D000818:Animals; D000070598:Anterior Cruciate Ligament Injuries; D002358:Cartilage, Articular; D010003:Osteoarthritis; D020370:Osteoarthritis, Knee; D051381:Rats; D012421:Rupture; D013977:Tibia
keywords: Acute injury; Bone; Microdamage; Non-invasive model; Remodeling; Subchondral