title: Post-Traumatic Osteoarthritis in Mice Following Mechanical Injury to the Synovial Joint.
abstract: We investigated the spectrum of lesions characteristic of post-traumatic osteoarthritis (PTOA) across the knee joint in response to mechanical injury. We hypothesized that alteration in knee joint stability in mice reproduces molecular and structural features of PTOA that would suggest potential therapeutic targets in humans. The right knees of eight-week old male mice from two recombinant inbred lines (LGXSM-6 and LGXSM-33) were subjected to axial tibial compression. Three separate loading magnitudes were applied: 6N, 9N, and 12N. Left knees served as non-loaded controls. Mice were sacrificed at 5, 9, 14, 28, and 56 days post-loading and whole knee joint changes were assessed by histology, immunostaining, micro-CT, and magnetic resonance imaging. We observed that tibial compression disrupted joint stability by rupturing the anterior cruciate ligament (except for 6N) and instigated a cascade of temporal and topographical features of PTOA. These features included cartilage extracellular matrix loss without proteoglycan replacement, chondrocyte apoptosis at day 5, synovitis present at day 14, osteophytes, ectopic calcification, and meniscus pathology. These findings provide a plausible model and a whole-joint approach for how joint injury in humans leads to PTOA. Chondrocyte apoptosis, synovitis, and ectopic calcification appear to be targets for potential therapeutic intervention.
authors.affiliation: Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, MO, USA.|Department of Cell Biology and Physiology, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, MO, USA.
authors.forename: Muhammad Farooq
authors.initials: MF
authors.lastname: Rai
authors.affiliation: Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, MO, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Duan
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Quirk
authors.affiliation: Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA.
authors.forename: Nilsson
authors.initials: N
authors.lastname: Holguin
authors.affiliation: Department of Physician Assistant Medicine, School of Graduate Health Studies, Lynchburg College, Lynchburg, VA, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Schmidt
authors.affiliation: Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, MO, USA.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Chinzei
authors.affiliation: Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, MO, USA.|Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Silva
authors.affiliation: Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, MO, USA.|Department of Cell Biology and Physiology, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, MO, USA.|Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Sandell
mesh_terms: D000818:Animals; D000070598:Anterior Cruciate Ligament Injuries / Q000150:complications* / Q000000981:diagnostic imaging* / Q000209:etiology; D017209:Apoptosis; D019902:Chondrocytes / Q000166:cytology; D004195:Disease Models, Animal; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000209:etiology*; D013314:Stress, Mechanical; D055114:X-Ray Microtomography / Q000379:methods