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Accelerated Calvarial Healing in Mice Lacking Toll-Like Receptor 4

Wang, D and Gilbert, JR and Cray, JJ and Kubala, AA and Shaw, MA and Billiar, TR and Cooper, GM (2012) Accelerated Calvarial Healing in Mice Lacking Toll-Like Receptor 4. PLoS ONE, 7 (10).

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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-1β, IL-6, TNF-α,TGF-β1, TGF-β3, PDGF and RANKL and lower expression level of RANK were detected at earlier time points (≤ postoperative 4 days); while higher expression levels of IL-1β 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. © 2012 Wang et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Wang, Ddaw112@pitt.eduDAW112
Gilbert, JRjrg101@pitt.eduJRG101
Cray, JJ
Kubala, AA
Shaw, MA
Billiar, TRbilliar@pitt.eduBILLIAR
Cooper, GMgmc8@pitt.eduGMC8
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorBereswill, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 10 October 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 10
DOI or Unique Handle: 10.1371/journal.pone.0046945
Schools and Programs: School of Medicine > Surgery
Swanson School of Engineering > Bioengineering
Refereed: Yes
PubMed ID: 23071670
Date Deposited: 18 Oct 2012 20:48
Last Modified: 02 Feb 2019 16:56
URI: http://d-scholarship.pitt.edu/id/eprint/16062

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