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

研究成果: Article同行評審

15 引文 斯高帕斯(Scopus)

摘要

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.

原文English
文章編號46050
期刊Scientific reports
7
DOIs
出版狀態Published - 2017 4月 10

All Science Journal Classification (ASJC) codes

  • 多學科

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