Pivotal role of Sirt6 in the crosstalk among ageing, metabolic syndrome and osteoarthritis

• Published in: Biochemical and biophysical research communications 2015-10, Vol.466 (3), p.319-326
• Main Authors: Ailixiding, Maierhaba, Aibibula, Zulipiya, Iwata, Munetaka, Piao, Jinying, Hara, Yasushi, Koga, Daisuke, Okawa, Atsushi, Morita, Sadao, Asou, Yoshinori
• Format: Article
• Language: English
• Subjects: Ageing; Aging; Animals; Apoptosis; Cartilage, Articular - pathology; Cellular Senescence; Chondrocytes - cytology; Chondrocytes - metabolism; Disease Progression; Gene Expression Profiling; Gene Expression Regulation; Glucose Intolerance; Glucose Tolerance Test; Glycosaminoglycans - chemistry; Hypertrophy; Inflammation - genetics; Inflammation - metabolism; Infrapatellar fat pad; Metabolic syndrome; Metabolic Syndrome - genetics; Metabolic Syndrome - metabolism; Mice; Mice, Transgenic; Osteoarthritis; Osteoarthritis - genetics; Osteoarthritis - metabolism; Osteophyte - metabolism; Serpin E2 - metabolism; Sirt6; Sirtuins - genetics; Sirtuins - physiology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2015.09.019

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. •Sirt6 ± mice fed HFD demonstrated promoted inflammation of the IPFP together with impaired glucose tolerance.•Enhanced inflammation of the IPFP was associated with accelerated OA progression in Sirt6 ± mice.•Endogenous Sirt6 was required for glycosaminoglycan expression in the chondrocyte.•PAI-1 protein expression in the articular chondrocytes was increased by Sirt6 deficiency.