title: Oxytocin prevents cartilage matrix destruction via regulating matrix metalloproteinases.
abstract: Degradation of the extracellular matrix type II Collagen (Col II) induced by proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) is an important hallmark of Osteoarthritis (OA). Oxytocin (OT) is a well-known neurohypophysical hormone that is synthesized in the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus. In this study, we have found that oxytocin receptor (OTR) was expressed in human primary chondrocytes, and the expression of which was reduced in chondrocytes from OA patients and in response to TNF-α treatment in a dose dependent manner. Notably, it was shown that TNF-α -induced degradation of Col II was restored by treatment with OT in a dose-dependent manner. In addition, TNF-α treatment (10 ng/mL) highly elevated the expression of MMP-1 and MMP-13 in SW1353 chondrocytes, which were reversed by OT in a dose dependent manner at both gene and protein expression levels. In addition, it was demonstrated that the JAK2/STAT1 pathway was involved in the restoration effects of OT in the degradation of Col II. Lastly, knockdown of OTR abolished the inhibitory effects of OT on the degradation of col II and the induction of MMP-1 and MMP-13 expression, suggesting the involvement of OTR. Our study implied the therapeutic potential of OT for cartilage degradation.
authors.affiliation: Department of Hip Injury, Luoyang Orthopedic Hospital of Henan Province Orthopedic Institute of Henan Province, 471002, China.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Wu
authors.affiliation: China Medical University, Henan Province, 471002, China.
authors.forename: Tongyu
authors.initials: T
authors.lastname: Wu
authors.affiliation: Shenqiu People's Hospital Henan Province, 471002, China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Hip Injury, Luoyang Orthopedic Hospital of Henan Province Orthopedic Institute of Henan Province, 471002, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Hip Injury, Luoyang Orthopedic Hospital of Henan Province Orthopedic Institute of Henan Province, 471002, China.
authors.forename: Honggan
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Hip Injury, Luoyang Orthopedic Hospital of Henan Province Orthopedic Institute of Henan Province, 471002, China. Electronic address: xiyaol12345@yeah.net.
authors.forename: Xiyao
authors.initials: X
authors.lastname: Li
mesh_terms: D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010121:Oxytocin / Q000378:metabolism* / Q000494:pharmacology; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D024043:Collagen Type II; C569600:OXTR protein, human; D034741:RNA, Small Interfering; D018045:Receptors, Oxytocin; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D014409:Tumor Necrosis Factor-alpha; D010121:Oxytocin; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: MMP-1; MMP-13; Osteoarthritis (OA); Oxytocin; Type II collagen