title: TREM-2 promotes acquired cholesteatoma-induced bone destruction by modulating TLR4 signaling pathway and osteoclasts activation.
abstract: Triggering receptor expressed on myeloid cells (TREM) has been broadly studied in inflammatory disease. However, the expression and function of TREM-2 remain undiscovered in acquired cholesteatoma. The expression of TREM-2 was significantly higher in human acquired cholesteatoma than in normal skin from the external auditory canal, and its expression level was positively correlated with the severity of bone destruction. Furthermore, TREM-2 was mainly expressed on dendritic cells (DCs). In human acquired cholesteatoma, the expression of proinflammatory cytokines (IL-1β, TNF-α and IL-6) and matrix metalloproteinases (MMP-2, MMP-8 and MMP-9) were up-regulated, and their expression levels were positively correlated with TREM-2 expression. Osteoclasts were activated in human acquired cholesteatoma. In an animal model, TREM-2 was up-regulated in mice with experimentally acquired cholesteatoma. TREM-2 deficiency impaired the maturation of experimentally acquired cholesteatoma and protected against bone destruction induced by experimentally acquired cholesteatoma. Additional data showed that TREM-2 up-regulated IL-1β and IL-6 expression via TLR4 instead of the TLR2 signaling pathway and promoted MMP-2 and MMP-8 secretion and osteoclast activation in experimentally acquired cholesteatoma. Therefore, TREM-2 might enhance acquired cholesteatoma-induced bone destruction by amplifying the inflammatory response via TLR4 signaling pathways and promoting MMP secretion and osteoclast activation.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, China.
authors.forename: Huaili
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Si
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, China.
authors.forename: Zhuohao
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine and Key Laboratory of Tropical Diseases Control, Ministry of Education Sun Yat-sen University, Guangzhou, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, China.
authors.forename: Suijun
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, China.
authors.forename: Ximing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, The third affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, China.
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, China.
authors.forename: Maojin
authors.initials: M
authors.lastname: Liang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001842:Bone and Bones / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010010:Osteoclasts / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C495345:TLR4 protein, human; C498715:TREM2 protein, human; D051197:Toll-Like Receptor 4