title: Reciprocal inhibition between miR-26a and NF-κB regulates obesity-related chronic inflammation in chondrocytes.
abstract: Obesity is causally linked to osteoarthritis (OA), with the mechanism being not fully elucidated. miRNAs (miRs) are pivotal regulators of various diseases in multiple tissues, including inflammation in the chondrocytes. In the present study, we for the first time identified the expression of miR-26a in mouse chondrocytes. Decreased level of miR-26a was correlated to increased chronic inflammation in the chondrocytes and circulation in obese mouse model. Mechanistically, we demonstrated that miR-26a attenuated saturated free fatty acid-induced activation of NF-κB (p65) and production of proinflammatory cytokines in chondrocytes. Meanwhile, NF-κB (p65) also suppressed miR-26a production by directly binding to a predicted NF-κB binding element in the promoter region of miR-26a. Finally, we observed a negative correlation between NF-κB and miR-26a in human patients with osteoarthritis. Thus, we identified a reciprocal inhibition between miR-26a and NF-κB downstream of non-esterified fatty acid (NEFA) signalling in obesity-related chondrocytes. Our findings provide a potential mechanism linking obesity to cartilage inflammation.
authors.affiliation: Department of Orthopaedics, Chengdu Military General Hospital. No. 270, Rongdu Avenue, Jinniu District, Chengdu, Sichuan 610083, PR China.
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Department of Nephrology and Rheumatology, Chengdu Military General Hospital. No. 270, Rongdu Avenue, Jinniu District, Chengdu, Sichuan 610083, PR China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wei
authors.affiliation: Department of Orthopaedics, Chengdu Military General Hospital. No. 270, Rongdu Avenue, Jinniu District, Chengdu, Sichuan 610083, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Kang
authors.affiliation: Department of Orthopaedics, Chengdu Military General Hospital. No. 270, Rongdu Avenue, Jinniu District, Chengdu, Sichuan 610083, PR China.
authors.forename: Da
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Chengdu Military General Hospital. No. 270, Rongdu Avenue, Jinniu District, Chengdu, Sichuan 610083, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Quan
authors.affiliation: Department of Orthopaedics, Chengdu Military General Hospital. No. 270, Rongdu Avenue, Jinniu District, Chengdu, Sichuan 610083, PR China.
authors.forename: Xianming
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Orthopaedics, Chengdu Military General Hospital. No. 270, Rongdu Avenue, Jinniu District, Chengdu, Sichuan 610083, PR China.
authors.forename: Xiling
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Chengdu Military General Hospital. No. 270, Rongdu Avenue, Jinniu District, Chengdu, Sichuan 610083, PR China.
authors.forename: Dongfa
authors.initials: D
authors.lastname: Liao
authors.affiliation: Department of Orthopaedics, Chengdu Military General Hospital. No. 270, Rongdu Avenue, Jinniu District, Chengdu, Sichuan 610083, PR China.
authors.forename: Jinbiao
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Chengdu Military General Hospital. No. 270, Rongdu Avenue, Jinniu District, Chengdu, Sichuan 610083, PR China Zhangbpaper@sina.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015992:Body Mass Index; D019902:Chondrocytes / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D010003:Osteoarthritis / Q000235:genetics; D011401:Promoter Regions, Genetic
chemical_list: D016207:Cytokines; D005230:Fatty Acids, Nonesterified; D035683:MicroRNAs; D016328:NF-kappa B; C528163:MIRN26 microRNA, human; C543693:Mirn26 microRNA, mouse
keywords: NF-κB; free fatty acid; miR-26a; osteoarthritis; proinflammatory cytokines