title: Overexpression of Sirtuin 6 suppresses cellular senescence and NF-κB mediated inflammatory responses in osteoarthritis development.
abstract: The aim of our study was to evaluate if Sirt6, a NAD + dependent histone deacetylase, plays a protective role in cartilage degeneration by suppressing cellular senescence and inflammatory responses. The expression level of sirt6 in normal and OA human knee articular cartilage was compared by immunofluorescence and western blotting. The effect of sirt6 overexpression on replicative senescence of chondrocytes and NF-κB target genes expression was evaluated. Histological assessment of OA mice knee joint was carried out to assess the in vivo effects of sirt6 overexpression on mice chondrocytes. We found sirt6 level was significantly decreased in the articular chondrocytes of OA patients compare to normal human. SA-β-gal staining revealed that overexpression of sirt6 suppressed replicative senescence of chondrocytes. Meanwhile, the expression of NF-κB dependent genes were significantly attenuated by sirt6 overxpression. Safranin-O staining and OARSI score of knee joint cartilage in OA mice revealed that Lenti-Sirt6 intraarticular injection could protect mice chondrocytes from degeneration. These data strongly suggest that overexpression of Sirt6 can prevent OA development by reducing both the inflammatory response and chondrocytes senescence. Therefore, the development of specific activators of Sirt6 may have therapeutic potential for the treatment of OA.
authors.affiliation: Department of orthopedics, Second affiliated hospital, Wenzhou medical university, Wenzhou, Zhejiang Province, China.
authors.forename: Yaosen
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of orthopedics, Second affiliated hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
authors.forename: Linwei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of orthopedics, Second affiliated hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of orthopedics, Second affiliated hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
authors.forename: Wanli
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of orthopedics, Second affiliated hospital, Wenzhou medical university, Wenzhou, Zhejiang Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Center for Stem Cell and Tissue Engineering, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of orthopedics, affiliated hospital of Yangzhou University School of Medicine, Yangzhou, Jiangsu Province, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of orthopedics, Second affiliated hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
authors.forename: Fangcai
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of orthopedics, Second affiliated hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Pan
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D016922:Cellular Senescence / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D024043:Collagen Type II / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D053583:Interleukin-1beta / Q000494:pharmacology; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D020370:Osteoarthritis, Knee / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D021381:Protein Transport / Q000187:drug effects; D037761:Sirtuins / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D024043:Collagen Type II; D053583:Interleukin-1beta; D016328:NF-kappa B; D051996:Transcription Factor RelA; C501860:Sirt6 protein, mouse; D053509:Matrix Metalloproteinase 13; C516592:SIRT6 protein, human; D037761:Sirtuins