title: Pivotal role of Sirt6 in the crosstalk among ageing, metabolic syndrome and osteoarthritis.
abstract: Osteoarthritis (OA) is a chronic degenerative joint disorder commonly associated with metabolic syndrome. As ageing and obesity has a great impact on the initiation/severity of OA, herein we sought to investigate the involvement of Sirt6 in the crosstalk between ageing and metabolic syndrome/OA. Sirt6 haploinsufficiency in mice promoted the expression of inflammatory cytokines in the IPFP. Enhanced inflammation of the IPFP in the aged Sirt6 ± HFD group was paralleled with accelerated OA change, including osteophyte growth and chondrocyte hypertrophy. Conversely, mesenchyme-specific Sirt6-deficient mice revealed both attenuated chondrocyte hypertrophy and proteoglycan synthesis, although chondrocyte senescence was enhanced as shown in the aged WT mice. Thus Sirt6 has key roles in the relationship among ageing, metabolic syndrome, and OA.
authors.affiliation: Department of Rehabilitation Medicine, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Maierhaba
authors.initials: M
authors.lastname: Ailixiding
authors.affiliation: Department of Orthopedics Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Zulipiya
authors.initials: Z
authors.lastname: Aibibula
authors.affiliation: Division of Veterinary Surgery, Nippon Veterinary and Life Science University, 1-7-1 Sakaiminamicho, Musashino-shi, Tokyo, 180-8602, Japan.
authors.forename: Munetaka
authors.initials: M
authors.lastname: Iwata
authors.affiliation: Department of Orthopedics Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Jinying
authors.initials: J
authors.lastname: Piao
authors.affiliation: Division of Veterinary Surgery, Nippon Veterinary and Life Science University, 1-7-1 Sakaiminamicho, Musashino-shi, Tokyo, 180-8602, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hara
authors.affiliation: Department of Orthopedics Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Koga
authors.affiliation: Department of Orthopedics Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okawa
authors.affiliation: Department of Rehabilitation Medicine, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Sadao
authors.initials: S
authors.lastname: Morita
authors.affiliation: Department of Orthopedics Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. Electronic address: aso.orth@tmd.ac.jp.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Asou
mesh_terms: D000375:Aging; D000818:Animals; D017209:Apoptosis; D002358:Cartilage, Articular / Q000473:pathology; D016922:Cellular Senescence; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D018450:Disease Progression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018149:Glucose Intolerance; D005951:Glucose Tolerance Test; D006025:Glycosaminoglycans / Q000737:chemistry; D006984:Hypertrophy; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D024821:Metabolic Syndrome / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism; D054850:Osteophyte / Q000378:metabolism; D058258:Serpin E2 / Q000378:metabolism; D037761:Sirtuins / Q000235:genetics / Q000502:physiology*
chemical_list: D006025:Glycosaminoglycans; D058258:Serpin E2; C511869:Serpine2 protein, mouse; C501860:Sirt6 protein, mouse; D037761:Sirtuins
keywords: Ageing; Infrapatellar fat pad; Metabolic syndrome; Osteoarthritis; Sirt6