title: Glatiramer acetate inhibits degradation of collagen II by suppressing the activity of interferon regulatory factor-1.
abstract: Pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) is considered to be the major one contributing to the process of development of osteoarthritis (OA).Interferon regulatory factor 1 (IRF-1) is an important transcriptional factor accounting for inflammation response induced by TNF-α. The physiological function of IRF-1 in OA is still unknown. In this study, we reported that the expression levels of IRF-1 in OA chondrocytes were significantly higher compared to those in normal chondrocytes, which was reversed by treatment with Glatiramer acetate (GA), a licensed clinical drug for treating patients suffering from multiple sclerosis (MS). We also found that GA is able to attenuate the upregulation of IRF-1 induced by TNF-α. Matrix metalloproteinase13 (MMP-13) is one of the downstream target genes of IRF-1, which can induce the degradation of collagen II. Importantly, our results indicated that GA suppressed the expression of MMP-13 as well as the degradation of collagen II. In addition, GA also suppressed TNF-α-induced production of NO and expression of iNOS. Finally, we found that the inhibition of STAT1 activation played a critical role in the inhibitory effects of GA on the induction of IRF-1 and MMP-13. These data suggest that GA might have a potential effect in therapeutic OA.
authors.affiliation: Department of Orthopedics, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China. Electronic address: luhd2022@163.com.
authors.forename: Huading
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Joint Surgery, Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Zeng
authors.affiliation: Department of Orthopedics, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
authors.forename: Liyi
authors.initials: L
authors.lastname: Lian
authors.affiliation: Department of Orthopedics, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
authors.forename: Yuhu
authors.initials: Y
authors.lastname: Dai
mesh_terms: D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D055785:Gene Knockdown Techniques; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D050856:Interferon Regulatory Factor-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis / Q000235:genetics; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D059748:Proteolysis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D024043:Collagen Type II; D007166:Immunosuppressive Agents; D050856:Interferon Regulatory Factor-1; D010455:Peptides; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D000068717:Glatiramer Acetate; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13
keywords: Collagen II; Glatiramer acetate (GA); Interferon regulatory factor-1 (IRF-1); Matrix metalloproteinase 13 (MMP-13); Osteoarthritis (OA); Tumor necrosis factor-alpha (TNF-α)