Therapeutic opportunities to prevent post-traumatic arthritis: Lessons from the natural history of arthritis after articular fracture.
An estimated 12% of patients seeking surgical intervention for symptomatic arthritis have an etiology of post-traumatic arthritis (PTA). The onset of PTA is rapid in the setting of articular fracture (AF). The investigation began with development of a murine model of a closed AF that develops PTA. In the process of characterizing this model a technique was developed for assessing quantitative synovial fluid biomarker concentrations. The work began with observations of the natural history of PTA development in the C57BL/6 strain of mice. A species of mice (MRL/MpJ) was found that is protected from PTA after AF. Further work identified key differences between mouse strains that did and did not develop PTA. This knowledge led to an intervention based on anti-cytokine (interleukin 1 receptor antagonist, (IL-1Ra) delivery in the C57BL/6 strain of mice that successfully prevented PTA following AF. This success in preventing PTA in the murine model has elucidated several important clinical implications: 1) Pro-inflammatory cytokines play an important role in the development of PTA after joint injury, 2) Pharmacologic intervention can lessen the severity of PTA after an AF, and 3) The murine AF model of joint injury provides a novel means of studying mechanisms of PTA development.
Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina.
Steven A
SA
Olson
Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina.
Bridgette D
BD
Furman
Duke Molecular Physiology Institute, Durham, North Carolina.|Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Virginia B
VB
Kraus
Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Janet L
JL
Huebner
Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina.|Department of Biomedical Engineering, Duke University, Durham, North Carolina.
Farshid
F
Guilak
D000818:Animals; D001168:Arthritis / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000517:prevention & control*; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007249:Inflammation / Q000503:physiopathology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism; D057072:Intra-Articular Fractures / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology; D007596:Joints / Q000503:physiopathology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010003:Osteoarthritis / Q000378:metabolism*; D013045:Species Specificity; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology; D055114:X-Ray Microtomography
D018925:Chemokines; D016207:Cytokines; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein
chemokine; cytokines; inflammation; injury; intra-articular fracture; macrophage; osteoarthritis; synovium; trauma