title: Exogenous glucosamine globally protects chondrocytes from the arthritogenic effects of IL-1beta.
abstract: The effects of exogenous glucosamine on the biology of articular chondrocytes were determined by examining global transcription patterns under normal culture conditions and following challenge with IL-1beta. Chondrocytes isolated from the cartilage of rats were cultured in several flasks either alone or in the presence of 20 mM glucosamine. Six hours later, one-half of the cultures of each group were challenged with 10 ng/ml IL-1beta. Fourteen hours after this challenge, RNA was extracted from each culture individually and used to probe microarray chips corresponding to the entire rat genome. Glucosamine alone had no observable stimulatory effect on the transcription of primary cartilage matrix genes, such as aggrecan, collagen type II, or genes involved in glycosaminoglycan synthesis; however, glucosamine proved to be a potent, broad-spectrum inhibitor of IL-1beta. Of the 2,813 genes whose transcription was altered by IL-1beta stimulation (P < 0.0001), glucosamine significantly blocked the response in 2,055 (approximately 73%). Glucosamine fully protected the chondrocytes from IL-1-induced expression of inflammatory cytokines, chemokines, and growth factors as well as proteins involved in prostaglandin E2 and nitric oxide synthesis. It also blocked the IL-1-induced expression of matrix-specific proteases such as MMP-3, MMP-9, MMP-10, MMP-12, and ADAMTS-1. The concentrations of IL-1 and glucosamine used in these assays were supraphysiological and were not representative of the arthritic joint following oral consumption of glucosamine. They suggest, however, that the potential benefit of glucosamine in osteoarthritis is not related to cartilage matrix biosynthesis, but is more probably related to its ability to globally inhibit the deleterious effects of IL-1beta signaling. These results suggest that glucosamine, if administered effectively, may indeed have anti-arthritic properties, but primarily as an anti-inflammatory agent.
authors.affiliation: Department of Orthopaedics and Rehabilitation, Gene Therapy Laboratory, University of Florida, College of Medicine, PO Box 100137, Gainesville, FL 32610-0137, USA. gouzej@ortho.ufl.edu
authors.forename: Jean-Noël
authors.initials: JN
authors.lastname: Gouze
authors.forename: Elvire
authors.initials: E
authors.lastname: Gouze
authors.forename: Mick P
authors.initials: MP
authors.lastname: Popp
authors.forename: Marsha L
authors.initials: ML
authors.lastname: Bush
authors.forename: Emil A
authors.initials: EA
authors.lastname: Dacanay
authors.forename: Jesse D
authors.initials: JD
authors.lastname: Kay
authors.forename: Padraic P
authors.initials: PP
authors.lastname: Levings
authors.forename: Kunal R
authors.initials: KR
authors.lastname: Patel
authors.forename: Jeet-Paul S
authors.initials: JP
authors.lastname: Saran
authors.forename: Rachael S
authors.initials: RS
authors.lastname: Watson
authors.forename: Steven C
authors.initials: SC
authors.lastname: Ghivizzani
mesh_terms: D000818:Animals; D001168:Arthritis / Q000378:metabolism*; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D005944:Glucosamine / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D053583:Interleukin-1beta; D005944:Glucosamine