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Media type:
E-Article
Title:
Glucosamine Activates Autophagy In Vitro and In Vivo
Contributor:
Caramés, Beatriz;
Kiosses, William B.;
Akasaki, Yukio;
Brinson, Diana C.;
Eap, William;
Koziol, James;
Lotz, Martin K.
Published:
Wiley, 2013
Published in:
Arthritis & Rheumatism, 65 (2013) 7, Seite 1843-1852
Language:
English
DOI:
10.1002/art.37977
ISSN:
0004-3591;
1529-0131
Origination:
Footnote:
Description:
ObjectiveAging‐associated changes in articular cartilage represent a main risk factor for osteoarthritis (OA). Autophagy is an essential cellular homeostasis mechanism. Aging‐associated or experimentally induced defects in autophagy contribute to organismal‐ and tissue‐specific aging, while enhancement of autophagy may protect against certain aging‐related pathologies such as OA. The objective of this study was to determine whether glucosamine can activate autophagy.MethodsChondrocytes from normal human articular cartilage were treated with glucosamine (0.1– 10 mM). Autophagy activation and phosphorylation levels of Akt, FoxO3, and ribosomal protein S6 were determined by Western blotting. Autophagosome formation was analyzed by confocal microscopy. Reporter mice systemically expressing green fluorescent protein (GFP) fused to light chain 3 (LC3) (GFP‐LC3–transgenic mice) were used to assess changes in autophagy in response to starvation and glucosamine treatment.ResultsGlucosamine treatment of chondrocytes activated autophagy, as indicated by increased LC3‐II levels, formation of LC3 puncta, and increased LC3 turnover. This was associated with glucosamine‐mediated inhibition of the Akt/FoxO3/mammalian target of rapamycin pathway. Administration of glucosamine to GFP‐LC3–transgenic mice markedly activated autophagy in articular cartilage.ConclusionGlucosamine modulates molecular targets of the autophagy pathway in vitro and in vivo, and the enhancement of autophagy is mainly dependent on the Akt/FoxO/mTOR pathway. These findings suggest that glucosamine is an effective autophagy activator and should motivate future studies on the efficacy of glucosamine in modifying aging‐related cellular changes and supporting joint health.