title: The effects of glucosamine sulfate on intervertebral disc annulus fibrosus cells in vitro.
abstract: BACKGROUND
  Glucosamine has gained widespread use among patients, despite inconclusive efficacy data. Inconsistency in the clinical literature may be related to lack of understanding of the effects of glucosamine on the intervertebral disc, and therefore, improper patient selection.
  
  
  OBJECTIVE
  The goal of our study was to investigate the effects of glucosamine on intervertebral disc cells in vitro under the physiological conditions of inflammation and mechanical loading.
  
  
  METHODS
  Controlled in vitro laboratory setting.
  
  
  METHODS
  Intervertebral disc cells isolated from the rabbit annulus fibrosus were exposed to glucosamine sulfate in the presence and absence of interleukin-1β and tensile strain. Outcome measures included gene expression, measurement of total glycosaminoglycans, new proteoglycan synthesis, prostaglandin E2 production, and matrix metalloproteinase activity. The study was funded by NIH/NCCAM, and the authors have no conflicts of interest.
  
  
  RESULTS
  Under conditions of inflammatory stimulation alone, glucosamine demonstrated a dose-dependent effect in decreasing inflammatory and catabolic mediators and increasing anabolic genes. However, under conditions of mechanical stimulation, although inflammatory gene expression was decreased, PGE2 was not. In addition, matrix metalloproteinase-3 gene expression was increased and aggrecan expression decreased, both of which would have a detrimental effect on matrix homeostasis. Consistent with this, measurement of total glycosaminoglycans and new proteoglycan synthesis demonstrated detrimental effects of glucosamine under all conditions tested.
  
  
  CONCLUSIONS
  These results may in part help to explain the conflicting reports of efficacy, as there is biological plausibility for a therapeutic effect under conditions of predominate inflammation but not under conditions where mechanical loading is present or in which matrix synthesis is needed.
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine, 3471 5th Ave, Suite 201, Pittsburgh, PA 15213, USA; The Ferguson Laboratory for Orthopaedic and Spine Research, University of Pittsburgh School of Medicine, 200 Lothrop Dr, Pittsburgh, PA 15213, USA. Electronic address: sowaga@upmc.edu.
authors.forename: Gwendolyn A
authors.initials: GA
authors.lastname: Sowa
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine, 3471 5th Ave, Suite 201, Pittsburgh, PA 15213, USA; The Ferguson Laboratory for Orthopaedic and Spine Research, University of Pittsburgh School of Medicine, 200 Lothrop Dr, Pittsburgh, PA 15213, USA.
authors.forename: J Paulo
authors.initials: JP
authors.lastname: Coelho
authors.affiliation: The Ferguson Laboratory for Orthopaedic and Spine Research, University of Pittsburgh School of Medicine, 200 Lothrop Dr, Pittsburgh, PA 15213, USA.
authors.forename: Lloydine J
authors.initials: LJ
authors.lastname: Jacobs
authors.affiliation: The Ferguson Laboratory for Orthopaedic and Spine Research, University of Pittsburgh School of Medicine, 200 Lothrop Dr, Pittsburgh, PA 15213, USA.
authors.forename: Kasey
authors.initials: K
authors.lastname: Komperda
authors.affiliation: The Ferguson Laboratory for Orthopaedic and Spine Research, University of Pittsburgh School of Medicine, 200 Lothrop Dr, Pittsburgh, PA 15213, USA.
authors.forename: Nora
authors.initials: N
authors.lastname: Sherry
authors.affiliation: The Ferguson Laboratory for Orthopaedic and Spine Research, University of Pittsburgh School of Medicine, 200 Lothrop Dr, Pittsburgh, PA 15213, USA.
authors.forename: Nam V
authors.initials: NV
authors.lastname: Vo
authors.affiliation: Department of Internal Medicine, Georgetown University School of Medicine, 3800 Reservoir Road, NW, Washington, DC 20007, USA.
authors.forename: Harry G
authors.initials: HG
authors.lastname: Preuss
authors.affiliation: Department of Obstetrics and Gynecology, University of Pittsburgh School of Medicine, 300 Halket St, Pittsburgh, PA 15213, USA.
authors.forename: Judith L
authors.initials: JL
authors.lastname: Balk
authors.affiliation: The Ferguson Laboratory for Orthopaedic and Spine Research, University of Pittsburgh School of Medicine, 200 Lothrop Dr, Pittsburgh, PA 15213, USA.
authors.forename: Jame D
authors.initials: JD
authors.lastname: Kang
mesh_terms: D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D005944:Glucosamine / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology; D007403:Intervertebral Disc / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D013314:Stress, Mechanical
chemical_list: D053674:Aggrecans; D006025:Glycosaminoglycans; D053583:Interleukin-1beta; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; D015232:Dinoprostone; D005944:Glucosamine
keywords: Gene expression; Glucosamine; Intervertebral disc degeneration; Matrix; Mechanical strain; Supplement