Comparison of inhibitory effects of glucosamine and mannosamine on bovine articular cartilage degradation in vitro.
OBJECTIVE
To compare the inhibitory effects of glucosamine and mannosamine on articular cartilage degradation and the effects on chondrocyte viability in vitro.


METHODS
Bovine articular cartilage explants.


METHODS
Explants were cultured in commercial medium for 48 hours. Cartilage was exposed to medium containing 10% fetal bovine serum, 10 microg of lipopolysaccharide/mL, and 0.5, 1.0, 2.5, 5.0, and 10.0 mg of glucosamine or mannosamine/mL for 24 hours. Nitric oxide (NO) production (nitrite concentration) and proteoglycan (PG) release (PG concentration) in media were measured. Cartilage extracts were analyzed via zymography to detect gelatinolytic activity. At the end of the experiment, explants were assessed for chondrocyte viability.


RESULTS
Addition of lipopolysaccharide resulted in increased NO production and PG release, but no increase in gelatinolytic activity, compared with controls. Glucosamine and mannosamine at concentrations as low as 0.5 mg/mL inhibited NO production. Glucosamine inhibited PG release at a minimum concentration of 1.0 mg/mL, whereas mannosamine inhibited PG release at a concentration of 0.5 mg/mL. Concentrations of glucosamine < or = 5.0 mg/mL did not adversely affect chondrocyte viability; however, at a concentration of 10.0 mg/mL, cell death was evident. Mannosamine had a toxic effect at a concentration of 5.0 mg/mL and was associated with pronounced chondrocyte death at a concentration of 10.0 mg/mL.


CONCLUSIONS
Glucosamine and mannosamine inhibit selected indices of bovine articular cartilage degradation at concentrations that do not affect chondrocyte viability. The potential for cytotoxic effects at higher concentrations underscores the importance of establishing appropriate dosage regimens for these aminomonosaccharides.
Mello
David M
DM
Department of Animal Science, College of Agriculture and Natural Resources, Michigan State University, East Lansing, MI 48824, USA.
Nielsen
Brian D
BD
Peters
Tonia L
TL
Caron
John P
JP
Orth
Michael W
MW
D000818:Animals; D002356:Cartilage / Q000187:drug effects*; D002417:Cattle; D002418:Cattle Diseases / Q000503:physiopathology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005944:Glucosamine / Q000494:pharmacology* / Q000627:therapeutic use; D006595:Hexosamines / Q000494:pharmacology* / Q000627:therapeutic use; D066298:In Vitro Techniques; D008070:Lipopolysaccharides; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy / Q000503:physiopathology / Q000662:veterinary*; D011509:Proteoglycans / Q000378:metabolism
D006595:Hexosamines; D008070:Lipopolysaccharides; D011509:Proteoglycans; C008322:mannosamine; D009569:Nitric Oxide; D020782:Matrix Metalloproteinases; D005944:Glucosamine