Oligogalacturonic acid inhibit bone resorption and collagen degradation through its interaction with type I collagen.
In this study, we showed that oligogalacturonic acid (OGA) purified from flax pectin inhibit in vitro osteoclastic bone resorption in a dose-dependent manner. The OGA inhibitory effect was neither linked to an effect on osteoclast apoptosis, nor to an inhibition of cathepsin K activity. By means of an in vitro collagen degradation assay we demonstrated that OGA prevented triple-helical type I collagen cleavage by cathepsin K in a dose and chain length dependent manner. This inhibition was not restricted to cathepsin K, since collagenolytic activity of other lysosomal cysteine proteases, such as cathepsin B and cathepsin L, as well as matrixmetalloproteinases such as MMP-9 were also inhibited. Interestingly, using non-collagen substrates we demonstrated that OGA does not inhibit the proteolytic activity of cathepsin B and L, suggesting that OGA inhibits collagen degradation without affecting the lysosomal cysteine enzyme proteolytic activity. Finally, preliminary study using surface plasmon resonance (SPR) showed that OGA binds to type I collagen but not to albumin, consistent with a specific effect on collagen. These results suggest that the observed inhibition of collagen degradation by OGA may be due to its ability to bind to the collagen molecule. By masking the collagen surface, OGA may render the collagen cleavage site less accessible to enzymes and thus prevent its enzymatic degradation.
Lion
Jean-Marc
JM
Unité INSERM ERI-12, Université de Picardie Jules Verne. 1, rue des Louvels, 80037 Amiens, France.
Mentaverri
Romuald
R
Rossard
Stéphanie
S
Jullian
Nathalie
N
Courtois
Bernard
B
Courtois
Josiane
J
Brazier
Michel
M
Mazière
Jean-Claude
JC
Kamel
Said
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001681:Biological Assay; D001862:Bone Resorption / Q000188:drug therapy*; D002401:Cathepsin B / Q000037:antagonists & inhibitors; D056657:Cathepsin K / Q000037:antagonists & inhibitors; D056668:Cathepsin L / Q000037:antagonists & inhibitors; D003094:Collagen / Q000187:drug effects*; D024042:Collagen Type I / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009844:Oligosaccharides / Q000494:pharmacology*; D010010:Osteoclasts / Q000187:drug effects; D011817:Rabbits
D024042:Collagen Type I; D009844:Oligosaccharides; C412763:oligogalacturonic acid; D003094:Collagen; D002401:Cathepsin B; D056668:Cathepsin L; D056657:Cathepsin K