No abstract

OBJECTIVEToll‐like receptor 4 (TLR4) is a member of highly conserved receptor family and is a critical activator of the innate immune response after tissue injury. TLR4 signaling has been shown to regulate both the immune response and bone metabolism during long‐bone fracture healing. Unlike defects in long bones, defects in the calvaria often do not heal. Here we tested the hypothesis that the inflammation driven by TLR4 activation limits the healing of calvarial defects.METHODSCircular bone defects were made in the parietal bones using a 1.8mm outer diameter trephine in WT (n=32) and TLR4−/− mice (n=24). Calvarial bone and surrounding soft tissues (e.g. skin and brain) were harvested and bone healing was assessed using histomorphology at postoperative days 0, 1, 2, 4, 7, 14, 21 and 28.RESULTSHistomorphometric analysis demonstrated significantly larger bone healing areas in TLR4−/− mice compared to WT mice on day7 (p<0.001). Similar levels of bone healing were observed by day 28 (p=0.070).CONCLUSIONSThese data are consistent with the hypothesis that TLR4 activation delays calvarial healing in mice. Further work is required to determine if this is due to inflammation driven by TLR4 activation.