The 5-lipoxygenase inhibitor BWA4C impairs osteoclastic resorption in a synchronized model of bone remodeling.
The role of leukotrienes on bone resorption was tested in a well-standardized model of bone remodeling by inhibiting their biosynthesis with BWA4C, a specific inhibitor of 5-lipoxygenase. After extraction of their upper molars unilaterally, 30 Wistar rats were divided into three groups; the first remained untreated (control group), the second received 80 mg/kg/day of BWA4C dissolved in polyethylene glycol 300 (experimental group), and the third received only the vehicle (sham-treated group). After four days of experiment, the animals were killed and the resorption profile was assessed along the antagonist mandibular buccal cortex. The main result was a dramatic decrease in the number of TRAP-positive mononucleated preosteoclasts in the experimental group (-69%, p < 0.0005 and p < 0.003 vs. the control and sham-treated groups, respectively). This drop was related to a significant decrease in the number of osteoclasts. Neither the activation of the differentiated osteoclasts nor their mean interface with the bone surface were affected by BWA4C. Concomitantly, the mast cell population residing near the vascular network limiting the periosteum was markedly and significantly increased by the treatment. These mast cells were mostly degranulating, i.e., were in a state of activation that we previously found to related to resorption. These data suggest (1) that the leukotrienes are involved in the recruitment of osteoclast progenitors, and/or their differentiation into preosteoclasts, and (2) that mast cells responded to leukotriene inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
Franchi-Miller
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Laboratoire de Biologie et Biomatériaux du Milieu Buccal et Osseux, Faculté de Chirurgie-Dentaire, Université René Descartes (Paris V), Montrouge, France.
Saffar
J L
JL
D000284:Administration, Oral; D000818:Animals; D044482:Benzeneacetamides; D016723:Bone Remodeling / Q000187:drug effects*; D001862:Bone Resorption / Q000188:drug therapy*; D002454:Cell Differentiation; D004195:Disease Models, Animal; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008334:Mandible / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D044482:Benzeneacetamides; D006877:Hydroxamic Acids; D016859:Lipoxygenase Inhibitors; C056614:N-(3-phenoxycinnamyl)acetohydroxamic acid; D007975:Leukotriene B4