| First Author | Wang D | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 10 | Pages | e46945 |
| PubMed ID | 23071670 | Mgi Jnum | J:192089 |
| Mgi Id | MGI:5464029 | Doi | 10.1371/journal.pone.0046945 |
| Citation | Wang D, et al. (2012) Accelerated calvarial healing in mice lacking Toll-like receptor 4. PLoS One 7(10):e46945 |
| abstractText | The bone and immune systems are closely interconnected. The immediate inflammatory response after fracture is known to trigger a healing cascade which plays an important role in bone repair. Toll-like receptor 4 (TLR4) is a member of a highly conserved receptor family and is a critical activator of the innate immune response after tissue injury. TLR4 signaling has been shown to regulate the systemic inflammatory response induced by exposed bone components during long-bone fracture. Here we tested the hypothesis that TLR4 activation affects the healing of calvarial defects. A 1.8 mm diameter calvarial defect was created in wild-type (WT) and TLR4 knockout (TLR4(-/-)) mice. Bone healing was tested using radiographic, histologic and gene expression analyses. Radiographic and histomorphometric analyses revealed that calvarial healing was accelerated in TLR4(-/-) mice. More bone was observed in TLR4(-/-) mice compared to WT mice at postoperative days 7 and 14, although comparable healing was achieved in both groups by day 21. Bone remodeling was detected in both groups on postoperative day 28. In TLR4(-/-) mice compared to WT mice, gene expression analysis revealed that higher expression levels of IL-1beta, IL-6, TNF-alpha,TGF-beta1, TGF-beta3, PDGF and RANKL and lower expression level of RANK were detected at earlier time points (</= postoperative 4 days); while higher expression levels of IL-1beta and lower expression levels of VEGF, RANK, RANKL and OPG were detected at late time points (> postoperative 4 days). This study provides evidence of accelerated bone healing in TLR4(-/-) mice with earlier and higher expression of inflammatory cytokines and with increased osteoclastic activity. Further work is required to determine if this is due to inflammation driven by TLR4 activation. |
