title: Joint degeneration following closed intraarticular fracture in the mouse knee: a model of posttraumatic arthritis.
abstract: Posttraumatic arthritis is one of the most frequent causes of disability following joint trauma. The objective of this study was to develop a model of a closed articular fracture in the mouse knee joint to quantify the temporal sequence of joint degeneration in a model of posttraumatic arthritis. Closed intraarticular fractures were created in the tibial plateau of adult mice (C57BL/6) using a computer-controlled materials testing system and a custom-built indenter tip. Tibial plateau fractures were classified and imaged over time using high-resolution digital radiography. Animals were sacrificed at 2, 4, 8, and 50 weeks following fracture, and the experimental and contralateral control limbs were harvested for histology and micro-computed tomography (microCT) analysis. By radiographic analysis, tibial plateau fractures closely resembled clinical fractures. More complex and comminuted fractures correlated to significantly higher fracture energies. Histologic analysis demonstrated progressive joint degeneration as measured by a modified Mankin scale, with fibrillation and loss of proteoglycan in the articular cartilage. Subchondral bone thickening was also observed in experimental joints. The induction of a closed intraarticular fracture of the mouse tibial plateau generated a reproducible and clinically relevant joint injury that progressed to osteoarthritis-like changes by histologic and microCT evaluations. The ability to induce joint degeneration without an osteotomy or open arthrotomy provides a valuable new model for studying the natural sequelae of posttraumatic arthritis. Notably, the use of a murine model will facilitate the use of genetically modified animals for the investigation of specific genes implicated in the pathology of posttraumatic arthritis.
authors.affiliation: Division of Orthopaedic Surgery, Department of Surgery, Duke University Medical Center, Box 3389, Durham, North Carolina 27710, USA.
authors.forename: Bridgette D
authors.initials: BD
authors.lastname: Furman
authors.forename: Jens
authors.initials: J
authors.lastname: Strand
authors.forename: W Chad
authors.initials: WC
authors.lastname: Hembree
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Ward
authors.forename: Farshid
authors.initials: F
authors.lastname: Guilak
authors.forename: Steven A
authors.initials: SA
authors.lastname: Olson
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000473:pathology; D004195:Disease Models, Animal; D007718:Knee Injuries / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology*; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology*; D011859:Radiography; D012720:Severity of Illness Index; D013978:Tibial Fractures / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology*