Fetuin-treatment reduces aseptic UHMWPE-particle-induced osteolysis

Max Daniel Kauther, University of Duisburg-Essen, Essen, Germany
Christina Polan, University of Duisburg-Essen, Essen, Germany
Rüdiger Schlepper, University of Duisburg-Essen, Essen, Germany
Gero Hilken, University of Duisburg-Essen, Essen, Germany
Marcus Jäger, University of Duisburg-Essen, Essen, Germany
Christian Wedemeyer, University of Duisburg-Essen, Essen, Germany

The particle-induced osteolysis, a chronic inflammatory reaction, is the major cause of total joint arthroplasty failure. Fetuin-A, a 60kDa protein of the cystatin-superfamily, accumulates in bone tissue and is a potent inhibitor of ectopic calcification. Furthermore, it influences the production of proinflammatory mediators. In this study, the effects of fetuin-A treatment were examined in a murine calvaria-mouse-model.

28 male C57BL/6 wild-type mice were distributed into four groups. Groups 1 and 3 were treated with a calvaria-sham-operation, in contrast to groups 2 and 4, which were treated with an application of 30µl ultra-high-molecular weight polyethylene particles (UHMWPE). Furthermore, groups 1 and 2 were treated with an intraperitoneal injection of NaCl, whereas groups 3 and 4 received an injection of 20mg bovine fetuin-A. The following analytical methods were performed including a laborchemical analysis, a measure of bone-volume along the midline suture with a three-dimensional micro-computer-tomography (micro-CT), and a histomorphometric and histopathological analysis of inflammation and bone resorption. The statistical analysis was expressed in means and standard errors. The level of significance was determined using one-way ANOVA and Student’s t-test.

Fetuin-A application in UHMWPE-treated mice causes a reduction of osteolysis in comparison to NaCl-treated mice in the measurement of bone volume in the centre of the midline suture (0.54mm³ ± 0.01mm³ vs. 0.51mm³ ± 0.04mm³; p<0.05). A treatment with UHMWPE (0.54mm³ ± 0.01mm³ (fetuin) and 0.51mm³ ± 0.04mm³ (NaCl)) induces a reduction of bone volume in both groups compared to sham-surgery groups (0.59mm³ ± 0.03mm³ (fetuin) und 0.57mm³ ± 0.03mm³ (NaCl)) (p<0.01). Additionally, the eroded surface of histomorphometric analysis results in less bone-resorption in fetuin-treatment (p<0.05). The histopathological analysis of both particles-treated groups presents a granulomatous scar tissue dominated by macrophages and UHMWPE-particles.

In this study, an application of fetuin-A under osteolytic conditions results in less bone resorption. Therefore, fetuin-A may have an osteoprotective function during the process of aseptic loosening.

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