Hdl Handle:
http://hdl.handle.net/10675.2/832
Title:
Accelerated Calvarial Healing in Mice Lacking Toll-Like Receptor 4
Authors:
Wang, Dan; Gilbert, James R.; Cray, James J. Jr; Kubala, Adam A.; Shaw, Melissa A.; Billiar, Timothy R.; Cooper, Gregory M.
Abstract:
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-1b, IL-6, TNF-a,TGF-b1, TGF-b3, PDGF and RANKL and lower expression level of RANK were detected at earlier time points (# postoperative 4 days); while higher expression levels of IL-1b 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.
Citation:
PLoS One. 2012 Oct 10; 7(10):e46945
Issue Date:
10-Oct-2012
URI:
http://hdl.handle.net/10675.2/832
DOI:
10.1371/journal.pone.0046945
PubMed ID:
23071670
PubMed Central ID:
PMC3468586
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Department of Oral Biology: Faculty Research and Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorWang, Danen_US
dc.contributor.authorGilbert, James R.-
dc.contributor.authorCray, James J. Jr-
dc.contributor.authorKubala, Adam A.-
dc.contributor.authorShaw, Melissa A.-
dc.contributor.authorBilliar, Timothy R.-
dc.contributor.authorCooper, Gregory M.-
dc.date.accessioned2012-10-26T20:35:13Z-
dc.date.available2012-10-26T20:35:13Z-
dc.date.issued2012-10-10en_US
dc.identifier.citationPLoS One. 2012 Oct 10; 7(10):e46945en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid23071670en_US
dc.identifier.doi10.1371/journal.pone.0046945en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/832-
dc.description.abstractThe 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-1b, IL-6, TNF-a,TGF-b1, TGF-b3, PDGF and RANKL and lower expression level of RANK were detected at earlier time points (# postoperative 4 days); while higher expression levels of IL-1b 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.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectImmunologyen_US
dc.subjectImmunityen_US
dc.subjectInflammationen_US
dc.subjectInnate Immunityen_US
dc.subjectImmune Responseen_US
dc.subjectModel Organismsen_US
dc.subjectAnimal Modelsen_US
dc.subjectMouseen_US
dc.subjectMedicineen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectMusculoskeletal Systemen_US
dc.subjectBoneen_US
dc.subjectPediatricsen_US
dc.subjectPediatric Orthopedicsen_US
dc.subjectSurgeryen_US
dc.subjectTrauma Surgeryen_US
dc.titleAccelerated Calvarial Healing in Mice Lacking Toll-Like Receptor 4en_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3468586en_US
dc.contributor.corporatenameDepartment of Oral Biology-
dc.contributor.corporatenameDepartment of Orthodontics-

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