Plastic Surgery Research Council
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Presenter: Melissa A Shaw, BS
Co-Authors: Wang D; Gilbert JR; Kubala AA; Shakir S; Losee JE; Billiar TR; Cooper GM
University of Pittsburgh

OBJECTIVE: Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) are members of a highly conserved receptor family and are critical activators of the innate immune response after tissue injury. TLR2 and TLR4 signaling have been shown to regulate both the immune response and bone metabolism. Here we tested the hypothesis that bone healing would be enhanced in mice lacking the TLR2 and TLR4 genes.

METHODS: Circular bone defects were made in the parietal bones using a 1.8mm outer diameter trephine in WT (n=42), TLR2-/- mice (n=28), and TLR4-/- mice (n=36). Calvarial bone and surrounding soft tissues (e.g. skin and brain) were harvested and bone healing was assessed at different time points using radiographic, histologic analyses, and qRT-PCR was performed to assess the expression of 8 genes related to bone repair.

RESULTS: 1) Radiographic and Histomorphometric analyses demonstrated accelerated calvarial healing in TLR4-/- mice compared to WT mice on day7 and day 14 (p<0.001), while a similar amount of bone formation was observed by day 28 between WT and TLR4-/- mice; significantly less bone healing was seen in TLR2-/- mice compared to WT and TLR4-/- mice by day 28. (p=0.070). 2) Differential expression of IL-1β, IL-6, BMP2 and TGFβ-β1 was observed between three groups of mice at early time points (3 hour, day 1 and day4).

CONCLUSIONS: These data suggest that TLR2 signaling is needed for calvarial healing in our murine model and TLR4 signaling might delay the healing process. Further work is required to elucidate the role of inflammation in signaling through these pathways on calvarial repair.

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