Knockdown of toll-like receptor 4 signaling pathways ameliorate bone graft rejection in a mouse model of allograft transplantation

Jeng Long Hsieh, Po Chuan Shen, Po-Ting Wu, I. Ming Jou, Chao-Liang Wu, Ai-Li Shiau, Chrong-Reen Wang, Hao Earn Chong, Shu Han Chuang, Jia Shiou Peng, Shih Yao Chen

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Abstract

Non-union occurring in structural bone grafting is a major problem in allograft transplantation because of impaired interaction between the host and graft tissue. Activated toll-like receptor (TLR) induces inflammatory cytokines and chemokines and triggers cell-mediated immune responses. The TLR-mediated signal pathway is important for mediating allograft rejection. We evaluated the effects of local knockdown of the TLR4 signaling pathway in a mouse segmental femoral graft model. Allografts were coated with freeze-dried lentiviral vectors that encoded TLR4 and myeloid differentiation primary response gene 88 (MyD88) short-hairpin RNA (shRNA), which were individually transplanted into the mice. They were assessed morphologically, radiographically, and histologically for tissue remodeling. Union occurred in autografted but not in allografted mice at the graft and host junctions after 4 weeks. TLR4 and MyD88 expression was up-regulated in allografted mice. TLR4 and MyD88 shRNAs inhibited TLR4 and MyD88 expression, which led to better union in the grafted sites. More regulatory T-cells in the draining lymph nodes suggested inflammation suppression. Local inhibition of TLR4 and MyD88 might reduce immune responses and ameliorate allograft rejection.

Original languageEnglish
Article number46050
JournalScientific reports
Volume7
DOIs
Publication statusPublished - 2017 Apr 10

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Toll-Like Receptor 4
Graft Rejection
Allografts
Transplantation
Bone and Bones
Toll-Like Receptors
Transplants
Bone Transplantation
Regulatory T-Lymphocytes
Thigh
Chemokines
Small Interfering RNA
Signal Transduction
Lymph Nodes
Cytokines
Inflammation
Genes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Hsieh, Jeng Long ; Shen, Po Chuan ; Wu, Po-Ting ; Jou, I. Ming ; Wu, Chao-Liang ; Shiau, Ai-Li ; Wang, Chrong-Reen ; Chong, Hao Earn ; Chuang, Shu Han ; Peng, Jia Shiou ; Chen, Shih Yao. / Knockdown of toll-like receptor 4 signaling pathways ameliorate bone graft rejection in a mouse model of allograft transplantation. In: Scientific reports. 2017 ; Vol. 7.
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abstract = "Non-union occurring in structural bone grafting is a major problem in allograft transplantation because of impaired interaction between the host and graft tissue. Activated toll-like receptor (TLR) induces inflammatory cytokines and chemokines and triggers cell-mediated immune responses. The TLR-mediated signal pathway is important for mediating allograft rejection. We evaluated the effects of local knockdown of the TLR4 signaling pathway in a mouse segmental femoral graft model. Allografts were coated with freeze-dried lentiviral vectors that encoded TLR4 and myeloid differentiation primary response gene 88 (MyD88) short-hairpin RNA (shRNA), which were individually transplanted into the mice. They were assessed morphologically, radiographically, and histologically for tissue remodeling. Union occurred in autografted but not in allografted mice at the graft and host junctions after 4 weeks. TLR4 and MyD88 expression was up-regulated in allografted mice. TLR4 and MyD88 shRNAs inhibited TLR4 and MyD88 expression, which led to better union in the grafted sites. More regulatory T-cells in the draining lymph nodes suggested inflammation suppression. Local inhibition of TLR4 and MyD88 might reduce immune responses and ameliorate allograft rejection.",
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Knockdown of toll-like receptor 4 signaling pathways ameliorate bone graft rejection in a mouse model of allograft transplantation. / Hsieh, Jeng Long; Shen, Po Chuan; Wu, Po-Ting; Jou, I. Ming; Wu, Chao-Liang; Shiau, Ai-Li; Wang, Chrong-Reen; Chong, Hao Earn; Chuang, Shu Han; Peng, Jia Shiou; Chen, Shih Yao.

In: Scientific reports, Vol. 7, 46050, 10.04.2017.

Research output: Contribution to journalArticle

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AU - Jou, I. Ming

AU - Wu, Chao-Liang

AU - Shiau, Ai-Li

AU - Wang, Chrong-Reen

AU - Chong, Hao Earn

AU - Chuang, Shu Han

AU - Peng, Jia Shiou

AU - Chen, Shih Yao

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