title: Knockdown of TREM-1 suppresses IL-1β-induced chondrocyte injury via inhibiting the NF-κB pathway.
abstract: Triggering receptor expressed on myeloid cells 1 (TREM-1) is a recently discovered molecule that modulates inflammatory responses. This study aimed to investigate the specific function of TREM-1 in chondrocytes and its association with the pathophysiology of osteoarthritis (OA). We observed upregulation of TREM-1 in OA cartilage compared to normal tissues. Knockdown of TREM-1 suppressed interleukin 1 beta (IL-1β)-induced extracellular matrix (ECM) metabolic imbalance, pro-inflammatory cytokine production, decrease in cell viability and apoptosis. Mechanistic analyses further revealed that IL-1β-induced activation of the NF-κB pathway is suppressed upon TREM-1 knockdown, similar to the effect of pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. TREM-1 expression was consistently increased in a mouse OA model in vivo, and its silencing led to inhibition of matrix metallopeptidase-13 (MMP-13) production, increased collagen type II synthesis and decreased NF-κB signaling. Our data collectively suggest that TREM-1 plays a critical in OA development through regulation of NF-κB signaling. Pharmacological inhibition of TREM-1 may therefore present an effective novel therapeutic approach for OA.
authors.affiliation: Department of Orthopedics, Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, China; Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Orthopedics, Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, China. Electronic address: doctor_qirongdong@163.com.
authors.forename: Qirong
authors.initials: Q
authors.lastname: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis; D002358:Cartilage, Articular / Q000378:metabolism*; D002470:Cell Survival; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010003:Osteoarthritis / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: D053583:Interleukin-1beta; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; C517262:TREM1 protein, mouse; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
keywords: Apoptosis; Chondrocytes; NF-κB; Osteoarthritis; TREM-1