Osteonecrosis induced by a single administration of low-dose lipopolysaccharide in rabbits

Citation
T. Irisa et al., Osteonecrosis induced by a single administration of low-dose lipopolysaccharide in rabbits, BONE, 28(6), 2001, pp. 641-649
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrynology, Metabolism & Nutrition","da verificare
Journal title
BONE
ISSN journal
8756-3282 → ACNP
Volume
28
Issue
6
Year of publication
2001
Pages
641 - 649
Database
ISI
SICI code
8756-3282(200106)28:6<641:OIBASA>2.0.ZU;2-X
Abstract
We succeeded in developing a novel rabbit model of nonsteroid and nontrauma tic osteonecrosis (ON) by use of a single- and low-dose lipopolysaccharide (LPS) injection. This model is simple and highly reproducible for the frequ ent development of multifocal and widespread ON lesions. Male adult Japanes e white rabbits intravenously injected with a single injection of 10 mug/kg body weight of LPS were histopathologically examined in the early phase (3 [n = 3], 5 [n = 3], and 24 h [n = 3]) and at 4 weeks (n = 22), Seventy-sev en percent of the rabbits developed multifocal ON 4 weeks after LPS injecti on. ON was also observed in the femoral and humeral condyle, The average pe rcentage of necrotic area/total area examined was 86.7 +/- 29.1% and 78.8 /- 16.7% in the proximal one third of both the femoral and humeral bones, r espectively, Organized thrombi in the intraosseous small-sized arteries and arterioles were frequently seen in and around the necrotic tissues. In the early phase, LPS treatment prominently induced thrombocytopenia, hyperlipi demia, and increased plasma levels of plasminogen activator inhibitor-1 (PA I-1), The plasma level of PAI-1 was significantly higher in the rabbits wit h ON than in those without ON (p < 0.01). The immunohistochemical expressio n of tissue factor was exaggerated in monocytes/macrophages and adipocytes in both the femoral and humeral bones of the LPS-treated rabbits. Hisstolog ically, marrow necrosis and fibrin thrombi could be observed at 24 h, In ad dition, pretreatment with an anticoagulant, warfarin potassium, significant ly decreased the incidence of LPS-induced ON (33%, n = 9, p < 0.05) associa ted with elongation of prothrombin time. The results of our study show that a single administration of low-dose lipopolysaccharide induces multifocal and widespread ON characterized by the pathophysiological participation of hypercoagulability in ON development. Therefore, this model would be useful for elucidating the pathogenesis of nonsteroid ON in humans especially inf lammatory hypercoagulability-induced as well as for developing preventive a nd therapeutic strategies, (C) 2001 by Elsevier Science Inc, All rights res erved.