Glucosamine activates autophagy in vitro and in vivo

Beatriz Caramés, William B. Kiosses, Yukio Akasaki, Diana C. Brinson, William Eap, James Koziol, Martin K. Lotz

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63 Citations (Scopus)

Abstract

Objective Aging-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. Methods Chondrocytes 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. Results Glucosamine 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. Conclusion Glucosamine 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.

Original languageEnglish
Pages (from-to)1843-1852
Number of pages10
JournalArthritis and rheumatism
Volume65
Issue number7
DOIs
Publication statusPublished - Jul 1 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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    Caramés, B., Kiosses, W. B., Akasaki, Y., Brinson, D. C., Eap, W., Koziol, J., & Lotz, M. K. (2013). Glucosamine activates autophagy in vitro and in vivo. Arthritis and rheumatism, 65(7), 1843-1852. https://doi.org/10.1002/art.37977