Distribution and Progression of Chondrocyte Damage in a Whole-Organ Model of Human Ankle Intra-Articular Fracture

Tochigi, Yuki; Buckwalter, Joseph A.; Martin, James A.; Hillis, Stephen L.; Peng Zhang; Vaseenon, Tanawat; Lehman, Abigail D.; Brown, Thomas D.
March 2011
Journal of Bone & Joint Surgery, American Volume;3/16/2011, Vol. 93-A Issue 6, p533
Academic Journal
Background: Despite the best current treatments, intra-articular fractures commonly cause posttraumatic osteoarthritis. In this disorder, death and dysfunction of chondrocytes associated with acute cartilage injury presumably plays an important role in triggering the pathomechanical cascade that eventualIy leads to whole-joint degeneration. Information regarding this cell-level cartilage injury, particularly at the whole-organ level in actual human joints, hasbeen lacking. In this study, the distribution and progression of fracture-associated cell-level cartilage damage were assessed using a novel whole-organ model of human ankle intra-articular fracture. Methods: Seven normal human ankles harvested immediately following amputation were subjected to a transarticular compressive impaction insult that mimicked an injury mechanism typical of tibial plafond fractures. For each ankle, sitespecific, time-dependent changes in chondrocyte viability in the fractured tibial surface were studied by means of live-dead assay, using a confocal laser-scanning microscope. Fractional chondrocyte death was measured at several time points, in the superficial zone of the cartilage in "fracture-edge" regions within 1 mm of the fracture lines, as well as in "nonfracture" regions more than 3 mm centrally away from the fracture lines. Results: All seven experimental fractures morphologically replicated tibial plafond fractures. Immediately post-fracture, superficial-zone chondrocyte death was significantly greater (p = 0.001) in fracture-edge regions (fractional cell death = 7.6%) than in non-fracture regions (1.6%). Progression of cell death over the next forty-eight hours was significantly faster in fracture-edge regions (p = 0.007), with the fractional cell death reaching 25.9%, which was again significantly higher (p < 0.001) than in non-fracture regions (8.6%). Conclusions: Cell-level cartilage damage in human intra-articular fractures was characterized by acute chondrocyte death that predominated along fracture lines and that spontaneously progressed in the forty-eight hours following injury. Clinical Relevance: Progressive chondrocyte damage along fracture lines appears to be a reasonable target of therapeutic treatment to preserve the whole-joint cartilage metabolism in intra-articular fractures, eventually to mitigate the risk of posttraumatic osteoarthritis.


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