N-acetyl muramyl dipeptide stimulation of bone resorption in tissue culture.
N-Acetyl-muramyl-L-alanyl-D-isoglutamine (MDP), a structurally defined fragment of bacterial peptidoglycan, stimulated significant release of previously incorporated 45Ca from fetal rat bones in tissue culture over the concentration range of 0.1 to 10.0 micrograms/ml. MDP-Stimulated bone resorption was not inhibited by the addition of the prostaglandin synthetase inhibitor indomethacin to the culture medium. MDP was neither mitogenic for nor stimulated the release of osteoclast-activating factor from cultured human peripheral blood mononuclear cells. Thus, MDP-stimulated bone resorption in vitro is mediated by a mechanism which is not dependent upon prostaglandins or osteoclast-activating factor. 6-O-Stearoyl-N-acetyl-muramyl-L-alanyl-D-isoglutamine, a lipophilic analog of MDP, was slightly more potent than MDP. Two diastereomers of MDP, N-acetyl-muramyl-L-alanyl-L-isoglutamine and N-acetyl-muramyl-D-alanyl-D-isoglutamine, which are inactive as adjuvants, were at least 1,000 times less active than MDP in stimulating bone resorption. The stereochemical specificity for bone-resorptive activity paralleled that required for adjuvant activity, macrophage activation, and activation of the reticuloendothelial system.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000818:Animals; D001862:Bone Resorption / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D046508:Culture Techniques; D006020:Glycopeptides / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology; D008222:Lymphokines / Q000096:biosynthesis; D008934:Mitogens; D051381:Rats; D013329:Structure-Activity Relationship
D006020:Glycopeptides; D008222:Lymphokines; D008934:Mitogens; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C008718:osteoclast activating factor; D007213:Indomethacin