Sulfated glycosaminoglycans and glucosamine may synergize in promoting synovial hyaluronic acid synthesis

Med Hypotheses. 2000 May;54(5):798-802. doi: 10.1054/mehy.1999.0954.


High-molecular-weight hyaluronic acid (HA) produced by the synovium may function physiologically to aid preservation of cartilage structure and prevent arthritic pain; both the size and concentration of HA in synovial fluid are diminished in osteoarthritis (OA). Glucosamine therapy for OA can be expected to increase synovial HA production by providing rate-limiting substrate. In addition, certain sulfated glycosaminoglycans and polysaccharides - including chondroitin sulfate (CS), dermatan sulfate, and pentosan polysulfate - stimulate synovial HA production, apparently owing to a hormone-like effect triggered by the binding of these polymers to membrane proteins of synovial cells. Surprisingly, a significant proportion of orally administered CS is absorbed as intact polymers - apparently by pinocytosis. These considerations may rationalize clinical studies concluding that oral CS provides slow-onset but durable pain relief and functional improvement in OA. The possibility that oral glucosamine and CS may interact in a complementary or synergistic fashion to improve synovial fluid HA content in OA should be assessed in clinical studies, and the potential of adjunctive CS administration to improve the clinical response achievable with optimal intakes of glucosamine should likewise be evaluated. In light of the fact that the synovium virtually functions as a 'placenta' for cartilage, focusing on synovium as the target for therapeutic intervention in OA may be a rational strategy.

MeSH terms

  • Administration, Oral
  • Drug Synergism
  • Glucosamine / pharmacology*
  • Glycosaminoglycans / administration & dosage
  • Glycosaminoglycans / chemistry
  • Glycosaminoglycans / pharmacology*
  • Humans
  • Hyaluronic Acid / biosynthesis*
  • Osteoarthritis / metabolism
  • Sulfates / chemistry*
  • Synovial Membrane / drug effects*
  • Synovial Membrane / metabolism


  • Glycosaminoglycans
  • Sulfates
  • Hyaluronic Acid
  • Glucosamine