title: Beneficial reward-to-risk action of glucosamine during pathogenesis of osteoarthritis.
abstract: OBJECTIVE
  Glucosamine is widely used to improve the symptoms and to delay the structural progression of osteoarthritis. However, its efficacy in osteoarthritis has been controversial and its underlying mechanism of action remains unclear. The aim of this study was to investigate the effects of glucosamine and the underlying mechanisms in human chondrocytes.
  
  
  METHODS
  Chondrocytes from normal human articular cartilage were treated with glucosamine (10-100 mM). Subsequently, cell death was analyzed by Annexin V staining and FACS and mitochondrial function was studied by measuring the mitopotential. Peroxisomal function was analyzed by BODIPY staining, and gene expression of PMP70 and acyl-CoA oxidase 1, by real-time PCR. Total lipids were analyzed by gas chromatography/mass spectrometry. Autophagy activation was determined by western blotting of beclin and light chain 3B. Autophagosome formation was analyzed by introduction of green fluorescent protein (GFP) LC3, and pexophagy was determined by introduction of mRFP-EGFP-SKL plasmids.
  
  
  RESULTS
  Treatment of chondrocytes with glucosamine exerts exposure time-dependent dual effects on apoptosis/autophagy. Short time exposure of glucosamine to chondrocytes activated autophagy, pexophagy, and peroxidation. On the other hand, long time exposure of glucosamine had opposite effects, namely accumulation of very long chain fatty acids and peroxisomal dysfunction.
  
  
  CONCLUSIONS
  We highlight the dual role of glucosamine in apoptosis/autophagy in human chondrocytes depending on exposure time. Although further research is required to fully understand the dual effects of glucosamine, dosage and duration of glucosamine treatment are clear contributing factors towards the line of beneficial reward-to-risk action.
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk, 570-749, Korea. yunokang@gmail.com.
authors.forename: Yeon-Ho
authors.initials: YH
authors.lastname: Kang
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk, 570-749, Korea. kasgami@daum.net.
authors.forename: Sujeong
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk, 570-749, Korea. chihyun433@gmail.com.
authors.forename: Chihyun
authors.initials: C
authors.lastname: Ahn
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk, 570-749, Korea. jinsoo85@naver.com.
authors.forename: Jinsoo
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk, 570-749, Korea. kdk80@daum.net.
authors.forename: Dongkyun
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk, 570-749, Korea. jineunjung@wku.ac.kr.|Integrated Omics Institute, Wonkwang University, Iksan, Chunbuk, 570-749, Korea. jineunjung@wku.ac.kr.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Jin
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D005944:Glucosamine / Q000009:adverse effects* / Q000494:pharmacology*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology; D020675:Peroxisomes / Q000187:drug effects / Q000378:metabolism
chemical_list: C063305:ABCD3 protein, human; D018528:ATP-Binding Cassette Transporters; D005227:Fatty Acids; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D005944:Glucosamine