Absence of posttraumatic arthritis following intraarticular fracture in the MRL/MpJ mouse.
OBJECTIVE
Posttraumatic arthritis is a frequent long-term complication of intraarticular fractures. A model of a closed intraarticular fracture in C57BL/6 mice that progresses to posttraumatic arthritis has been developed. The MRL/MpJ mouse has shown unique regenerative abilities in response to injury. The objective of this study was to determine if the MRL/MpJ mouse is protected from posttraumatic arthritis after intraarticular fractures.


METHODS
Intraarticular fractures were created in MRL/MpJ mice and C57BL/6 control mice (n = 16 each). Limbs were analyzed for posttraumatic arthritis 4 and 8 weeks after fracture using microfocal computed tomography bone morphology, subchondral bone thickness evaluation, and histologic evaluation of cartilage degeneration. Serum cytokines and biomarkers were measured after the mice were killed.


RESULTS
Intraarticular fractures were successfully created in all 32 mice. In the experimental fractured limbs, C57BL/6 mice had a decrease in bone density, increased subchondral bone thickness, and increased cartilage degeneration compared with normal contralateral control limbs. In the MRL/MpJ mice, no differences in bone density, subchondral bone thickness, or histologic grading of cartilage degeneration were seen between fractured and contralateral control limbs. Cytokine analysis showed lower systemic levels of the proinflammatory cytokine interleukin-1alpha (IL-1alpha) and higher levels of the antiinflammatory cytokines IL-4 and IL-10 in the MRL/MpJ mice.


CONCLUSIONS
This study shows that the MRL/MpJ mouse is relatively protected from posttraumatic arthritis after intraarticular fracture. Further investigation into the mechanism involved in this response will hopefully provide new insight into the pathogenesis, prevention, and treatment of posttraumatic arthritis after intraarticular fracture.
Ward
Benjamin D
BD
Duke University Medical Center, Durham, North Carolina 27710, USA.
Furman
Bridgette D
BD
Huebner
Janet L
JL
Kraus
Virginia B
VB
Guilak
Farshid
F
Olson
Steven A
SA
D000818:Animals; D001168:Arthritis / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001861:Bone Regeneration / Q000235:genetics / Q000502:physiology; D002356:Cartilage / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D050723:Fractures, Bone / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D016753:Interleukin-10 / Q000097:blood; D053582:Interleukin-1alpha / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D007596:Joints / Q000293:injuries*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains
D015415:Biomarkers; D053582:Interleukin-1alpha; D016753:Interleukin-10; D015847:Interleukin-4