title: Bortezomib prevents the expression of MMP-13 and the degradation of collagen type 2 in human chondrocytes.
abstract: The structural backbone of extracellular matrix in cartilage is the collagen fibril, which is mainly composed of type II collagen. A measurable increase in type II collagen denaturation and degradation has been found in early Osteoarthritis (OA). Pro-inflammatory cytokine such as TNF-α produced in OA cartilage induced the expression of matrix metalloproteinase-13 (MMP-13), which targets and degrades type II collagen. Bortezomib is a proteasome inhibitor approved by the FDA for treatment of multiple myeloma and mantel cell lymphoma. The effects of bortezomib in OA have not been reported before. In this study, we found that bortezomib is able to suppress the degradation of type II collagen induced by TNF-α in human chondrocytes. Mechanistically, bortezomib treatment inhibits the expression of IRF-1 through blunting JAK2/STAT1 pathway, thereby prevents the induction of MMP-13 as well as the degradation of type II collagen. Our findings suggest the therapeutic potentials of bortezomib in patients with OA.
authors.affiliation: Department of Orthopaedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Orthopaedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Weikai
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Fengjing
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Orthopaedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. Electronic address: anchen066@yeah.net.
authors.forename: Anmin
authors.initials: A
authors.lastname: Chen
mesh_terms: D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D024043:Collagen Type II / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000235:genetics* / Q000378:metabolism; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D059748:Proteolysis / Q000187:drug effects; D011719:Pyrazines / Q000494:pharmacology*; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D001897:Boronic Acids; D024043:Collagen Type II; D050856:Interferon Regulatory Factor-1; D061988:Proteasome Inhibitors; D011719:Pyrazines; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D014409:Tumor Necrosis Factor-alpha; D000069286:Bortezomib; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D053509:Matrix Metalloproteinase 13; D046988:Proteasome Endopeptidase Complex
keywords: Interferon response factor-1 (IRF-1); Matrix metalloproteinase-13; Osteoarthritis; TNF-α; Type II collagen