title: Knockdown of toll-like receptor 4 signaling pathways ameliorate bone graft rejection in a mouse model of allograft transplantation.
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.
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan.
authors.forename: Jeng-Long
authors.initials: JL
authors.lastname: Hsieh
authors.affiliation: Department of Orthopedics, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan.
authors.forename: Po-Chuan
authors.initials: PC
authors.lastname: Shen
authors.affiliation: Department of Orthopedics, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Po-Ting
authors.initials: PT
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: I-Ming
authors.initials: IM
authors.lastname: Jou
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chao-Liang
authors.initials: CL
authors.lastname: Wu
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ai-Li
authors.initials: AL
authors.lastname: Shiau
authors.affiliation: Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chrong-Reen
authors.initials: CR
authors.lastname: Wang
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan.
authors.forename: Hao-Earn
authors.initials: HE
authors.lastname: Chong
authors.affiliation: Department of Pharmacology, Institute for Drug Evaluation Platform, Development Center for Biotechnology, Taipei, Taiwan.
authors.forename: Shu-Han
authors.initials: SH
authors.lastname: Chuang
authors.affiliation: Department of Nursing, Chung-Jen Junior College of Nursing, Health Sciences and Management, Chiayi, Taiwan.
authors.forename: Jia-Shiou
authors.initials: JS
authors.lastname: Peng
authors.affiliation: Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shih-Yao
authors.initials: SY
authors.lastname: Chen
mesh_terms: D064591:Allografts / Q000378:metabolism*; D000818:Animals; D016025:Bone Transplantation; D004195:Disease Models, Animal; D005269:Femur / Q000637:transplantation; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006084:Graft Rejection / Q000378:metabolism*; D016086:Lentivirus / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014184:Transplantation, Homologous; D014945:Wound Healing
chemical_list: D053594:Myeloid Differentiation Factor 88; D051197:Toll-Like Receptor 4