RRC ID 27895
著者 Caramés B, Kiosses WB, Akasaki Y, Brinson DC, Eap W, Koziol J, Lotz MK.
タイトル Glucosamine activates autophagy in vitro and in vivo.
ジャーナル Arthritis Rheum
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.
巻・号 65(7)
ページ 1843-52
公開日 2013-7-1
DOI 10.1002/art.37977
PMID 23606170
PMC PMC3772083
MeSH Animals Autophagy / drug effects* Cartilage, Articular / cytology* Chondrocytes / drug effects* Chondrocytes / physiology Forkhead Box Protein O3 Forkhead Transcription Factors / drug effects Forkhead Transcription Factors / metabolism Glucosamine / pharmacology* Humans Liver / drug effects Liver / metabolism Mice Mice, Transgenic Microscopy, Confocal Microtubule-Associated Proteins / drug effects Microtubule-Associated Proteins / metabolism Phosphorylation / drug effects Proto-Oncogene Proteins c-akt / drug effects Proto-Oncogene Proteins c-akt / metabolism Ribosomal Protein S6 / drug effects Ribosomal Protein S6 / metabolism Signal Transduction / drug effects* TOR Serine-Threonine Kinases / drug effects TOR Serine-Threonine Kinases / metabolism
引用数 58
WOS 分野 RHEUMATOLOGY
リソース情報
実験動物マウス RBRC00806