title: Cilostazol prevents the degradation of collagen type II in human chondrocytes.
abstract: The alteration of extracellular matrix (ECM) in cartilage during the pathological development of Osteoarthritis (OA) changes the biomechanical environment of chondrocytes, which further drives the progression of the disease in the presence of inflammation. Healthy cartilage matrix mainly contains collagen type II, which is degraded by matrix metalloproteinase13 (MMP13), an important molecules responsible for joint damage in OA. Cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2-(1H)-quinolinone) is a medication approved by the US Food and Drug Administration and used in the alleviation of the symptom of intermittent claudication in individuals with peripheral vascular disease. In this study, we reported that cilostazol is able to suppress the degradation of type II collagen in human chondrocytes induced by IL-1β. Mechanistically, cilostazol treatment leads to inhibiting the expression of IRF-1, thereby prevents the induction of MMP-13. Signal transducers and activator of transcription 1 (STAT1) has been reported to play an essential role in regulating the activation of IRF-1. Our results indicated that cilostazol suppresses the activation of STAT1 by mitigating the phosphorylation of STAT1 at Ser727 and tyrosine phosphorylation of STAT1 at position 701 (Tyr701).
authors.affiliation: Department of Spine and Joint, The 2nd Hospital, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Ear-Nose-Throat, The 2nd Hospital, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Weibiao
authors.initials: W
authors.lastname: Kang
authors.affiliation: Department of Spine and Joint, The 2nd Hospital, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Spine and Joint, The 2nd Hospital, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Guanfeng
authors.initials: G
authors.lastname: Yao
authors.affiliation: Department of Spine and Joint, The 2nd Hospital, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, The 1st Hospital, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Bizhen
authors.initials: B
authors.lastname: Cheng
authors.affiliation: Department of Spine and Joint, The 2nd Hospital, Shantou University Medical College, Shantou, Guangdong 515041, China. Electronic address: kongkm55@yeah.net.
authors.forename: Kangmei
authors.initials: K
authors.lastname: Kong
mesh_terms: D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D000077407:Cilostazol; D024043:Collagen Type II / Q000378:metabolism*; D006801:Humans; D050856:Interferon Regulatory Factor-1; D053583:Interleukin-1beta / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D024043:Collagen Type II; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D053583:Interleukin-1beta; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D013777:Tetrazoles; D053509:Matrix Metalloproteinase 13; D000077407:Cilostazol
keywords: Cilostazol; Collagen type II; IRF-1; MMP-13; Osteoarthritis (OA); STAT1