Low-dose doxycycline prevents inflammatory bone resorption in rats

Abstract

Matrix metalloproteinases (MMP) are considered to be key initiators of collagen degradation, thus contributing to bone resorption in inflammatory diseases. We determined whether subantimicrobial doses of doxycycline (DX) (£10 mg kg -1 day -1 ), a known MMP inhibitor, could inhibit bone resorption in an experimental periodontitis model. Thirty male Wistar rats (180-200 g) were subjected to placement of a nylon thread ligature around the maxillary molars and sacrificed after 7 days. Alveolar bone loss (ABL) was measured macroscopically in one hemiarcade and the contralateral hemiarcade was processed for histopathologic analysis. Groups of six animals each were treated with DX (2.5, 5 or 10 mg kg -1 day -1 , sc, 7 days) and compared to nontreated (NT) rats. NT rats displayed significant ABL, severe mononuclear cell influx and increase in osteoclast numbers, which were significantly reduced by 5 or 10 mg kg -1 day -1 DX. These data show that DX inhibits inflammatory bone resorption in a manner that is independent of its antimicrobial properties.

Efficacy of subantimicrobial-dose doxycycline against nitrosative stress in chronic periodontitis

“…The role of NO in modulating PMN infiltration may vary with the type of tissue and the presence of inflammatory disease, but it is thought that low levels of NO reduce inflammatory cell adhesion to the endothelium, and high levels of NO stimulate it. Like other studies, our findings at baseline confirm that high levels of NO induced by iNOS stimulate leukocyte accumulation within the periodontal tissue and reduce clinical periodontal indices [14,19,33] . Consequently, in both groups, iNOS reduction diminished inflammatory cell infiltrate, and these were correlated with changes in the periodontal clinical parameters.…”

“…The inflammatory cell influx, independent for neutrophils and mononuclear cells, was evaluated by counting the number of cells in 20 high-power fields (Cell B basic imaging software, Olympus), and defined as: 0 (0-5 inflammatory cells); 1 (5-10 inflammatory cells); 2 (10-30 inflammatory cells); or 3 (more than 30 inflammatory cells) [12,[17][18][19] .…”

Diabetes Enhances Periodontal Bone Loss through Enhanced Resorption and Diminished Bone Formation

“…To examine separately the impact of diabetes on periodontal bone loss and the formation of new bone following resorption, we carried out studies in a model where a ligature was placed around a molar tooth and the ensuing inflammation, loss of attachment, and bone were measured over a seven-day period (Bezerra et al, 2002;Gaspersic et al, 2003). This model was chosen since it mimics several features of human periodontitis, including the formation of an inflammatory infiltrate, loss of attachment, and loss of alveolar bone.…”

“…This model was chosen since it mimics several features of human periodontitis, including the formation of an inflammatory infiltrate, loss of attachment, and loss of alveolar bone. Moreover, these features are dependent upon a bacteria-induced host response, as indicated by decreased loss of attachment and reduced bone resorption in rats treated with chlorhexidine, antibiotics, or prostaglandin inhibitors (Weiner et al, 1979;Kenworthy and Baverel, 1981;Bezerra et al, 2002). Interestingly, bone loss and inflammation are accelerated by the administration of IL-1β or TNF-α (Koide et al, 1995;Gaspersic et al, 2003), which is consistent with results obtained in non-human primates, demonstrating that inhibition of these cytokines reduces alveolar bone loss (Assuma et al, 1998;Delima et al, 2002).…”

Sıçanlarda Doksisiklinin Kimyasal Peritonite Bağlı Peritoneal Fibrozis Gelişimi Üzerine Etkisinin İncelenmesi

“…Literatürde bu antibiyotik grubunun MMP inhibisyonu ile ilgili deneysel hayvan çalışmaları vardır (20)(21)(22), ancak kimyasal peritonite bağlı fibrozis gelişimi üzerine etkisi ile ilgili klinik ve deneysel hayvan çalışması yoktur.…”