[Regulation of osteoclastic resorption by prostanoids in vivo].
Prostanoids, and particularly prostaglandins (PGs) E, are potent mediators of bone resorption. However the actual role(s) of these agents in osteoclastic resorption is (are) not yet known. In an attempt to approach the role of prostanoids in the events leading to resorption itself, we used two different animal models. We showed that indomethacin, an inhibitor of prostanoid biosynthesis, drastically reduced osteoclastic resorption at the dose of 7 mg/kg/d in the two models. This effect was dose-dependent as resorption inhibition increased by increasing the dose of indomethacin. However the effect was already significant at the lower dose (2 mg/kg/d). The total number of osteoclasts in the site was according by reduced, showing the involvement of the prostanoids in the events preceding and/or regulating the fusion of the mononucleated preosteoclasts into multinucleated osteoclasts. The calculation of the ratio active/inactive osteoclasts indicated that the activation (i.e. access to the bone surface) of the osteoclast, was prostanoid-dependent; indeed the ratio systematically decreased in the indomethacin-treated animals in the two models. We also observed that the inhibition was not sustained in time as resorption recovered, probably through the starting of PG-independent metabolic pathways. However this starting was rather slow and these pathways apparently were less affective than the PG-dependent ones since the intrinsic activity of the differentiated osteoclasts was significantly reduced.
Saffar
J L
JL
Laboratoire de Biologie et Biomatériaux du Milieu buccal et osseux, Faculté de Chirurgie Dentaire, Université Paris V, Montrouge, France.
Lasfargues
J J
JJ
Leroux
P
P
Guez
D
D
D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy*; D002454:Cell Differentiation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010010:Osteoclasts / Q000166:cytology; D011458:Prostaglandins E / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D011458:Prostaglandins E; D007213:Indomethacin
Régulation de la résorption ostéoclastique par les prostanoïdes in vivo.