Effects of long-term cyclosporin therapy on the periodontium of rats

Background: The treatment of cyclosporin A triggers an early bone loss and gingival overgrowth. There is a lack of studies exploring the effects of long-term cyclosporin A therapy on alveolar bone homeostasis and gingival tissue. Objective: The purpose of this study was to evaluate the effects of long-term therapy with cyclosporin A on the gingival tissue and on the alveolar bone metabolism in rats. Materials and methods: Rats were treated for 60, 120, 180 and 240 days with a daily subcutaneous injection of 10 mg/kg body weight of cyclosporin A. At the end of experimental periods, animals were killed and the serum calcium (Ca2+) and alkaline phosphatase levels were measured in all groups. After histological processing, the oral epithelium and the connective tissue, as well as volume densities of alveolar bone (Vb) and multinucleated osteoclasts (Vo), were assessed at the region of the lower first molars. Results: Significant increases in the serum alkaline phosphatase were observed in those groups that received cyclosporin A therapy. After 60 and 120 days of the treatment with cyclosporin A, evident gingival overgrowth associated with a significant increase of epithelium and connective tissue was observed, as well as a decrease of the densities of bone and an increase of densities of osteoclasts. After 180 and 240 days of the treatment, there was a reduction of the gingival overgrowth associated with significant decreases of epithelium and connective tissue, as well as an increase of bone densities and a decrease of osteoclasts. Conclusion: Within the limits of this experimental study, it can be concluded that the deleterious periodontal effects of cyclosporin A administration may be time-related side-effects. © Blackwell Munksgaard, 2004.

Homeostase do cálcio e marcadores do metabolismo ósseo no hipertireoidismo felino - Revisão

Hyperthyroidism is the most frequent endocrine disease in old-aged cats. It is a illness provoked by the excess of circulating thyroid hormones. Hyperthyroidism causes alteration in bone metabolism with predominance of activity resorption. The evaluation of bone metabolism can be made by measuring serum and urinary markers of bone metabolism or bone mineral densitometry. Osteoblasts are responsible cells for bone formation while the osteoclasts are for resorption. In physiological situation osteoblastic and osteoclastic activities are in balance. Markers of bone formation express the osteoblastic activity and markers of the osseous resorption the osteoclástica activity. Markers of bone turnover are important in the diagnosis and prognostic of muscle-skeletal disease, as well as in the accompaniment of therapy. It is fundamental do carry on studies on the influence of feline hyperthyroidism on markers of bone formation and resorption in bone turnover to comprise pathophysiologic mechanism of bone alterations.

Microwave-induced fast decalcification of rat bone for electron microscopic analysis: An ultrastructural and cytochemical study

Bone decalcification is a time-consuming process. It takes weeks and preservation of the tissue structure depends on the quality and velocity of the demineralization process. In the present study, a decalcification methodology was adapted using microwaving to accelerate the decalcification of rat bone for electron microscopic analysis. The ultrastructure of the bone decalcified by microwave energy was observed. Wistar rats were perfused with paraformaldehyde and maxillary segments were removed and fixed in glutaraldehyde. Half of specimens were decalcified by conventional treatment with immersion in Warshawsky solution at 4oC during 45 days, and the other half of specimens were placed into the beaker with 20 mL of the Warshawsky solution in ice bath and thereafter submitted to irradiation in a domestic microwave oven (700 maximum power) during 20 s/350 W/±37°C. In the first day, the specimens were irradiated 9 times and stored at 40°C overnight. In the second day, the specimens were irradiated 20 times changing the solution and the ice after each bath. After decalcification, some specimens were postfixed in osmium tetroxide and others in osmium tetroxide and potassium pyroantimonate. The specimens were observed under transmission electron microscopy. The results showed an increase in the decalcification rate in the specimens activated by microwaving and a reduction of total experiment time from 45 days in the conventional method to 48 hours in the microwave-aided method.

Effects of Long-Term FK 506 Therapy on the Alveolar Bone and Cementum of Rats

Cyclosporine (CsA) and tacrolimus (FK 506) exert complex, incompletely understood actions on bone. The objective of the study was to evaluate the effects of long-term tacrolimus therapy on the periodontium. Rats were treated for 60, 120, 180, and 240 days with daily subcutaneous injections of 1 mg/kg body weight of FK 506. After the experimental period, we obtained serum levels of calcium and alkaline phosphatase (ALP). After histological processing, the alveolar bone and cementum, as well as volume densities of bone (Vb) and osteoclasts (Vo), were assessed at the regions of the lower first molar. There was a tendency toward a statistically significant decrease in ALP levels with FK 506; however, serum calcium levels increased during the long periods. At 60, 180, and 240 days of treatment with FK 506, we did not observe Vb and Vo alterations. At 120 days of treatment, there was an evident decrease in Vb, but it did not show alveolar bone loss. We did not observe any alterations of cementum among rats treated with FK 506. It may be concluded that FK 506 administration did not induce side effects on the periodontium. © 2009 Elsevier Inc. All rights reserved.

Marginal resection for treatment of mandibular osteomyelitis associated with osteopetrosis: Case report

Osteopetrosis (OP) is a rare hereditary disorder characterized by a dysfunction of the osteoclasts that impairs bone resorption, which together with the normal osteoblastic activity forms intense bone sclerosis with reduction of marrow. A common complication that arises, most frequently, as a result of tooth extraction is mandibular osteomyelitis. There is no consensus on the literature about the treatment of this infection in an osteopetrotic patient, therefore, the purpose of this paper is to report a case of marginal resection for treatment of mandibular osteomyelitis in an osteopetrotic patient and discuss relevant features of this procedure. © 2010 European Association for Cranio-Maxillo-Facial Surgery.

Alterações da densidade mineral óssea em vértebras de ratos wistar submetidos à ausência de carga nos membros pélvicos

The suspension of rats by the tail model is used to investigate the behavior of bone in animals unable to move around. Bone is an adaptative tissue that develops in structure and function, among other factors, in response to mechanical forces applied to it and metabolic demands that it will suffer. The absence of mechanical forces and deformation of bone that occurs causes a decrease in calcium deposition in the absence of stimuli on osteoblasts and osteocytes, favoring the action of osteoclasts, making bones weak and brittle. Therefore, the mechanical action is necessary to stimulate local bone response and thus provide growth and remodeling. The aim of this study was to evaluable by radiographic densitometry, the tail suspension for 15 and 36 days alter the bone mineral density of cervical vertebrae (C3), thoracic (T6) and lumbar (L1 and L3) of Wistar rats. Thirty Rattus norvegicus albinus, adult, male, Wistar strain, average body mass ± 350g, were divided into 3 groups: control (n = 10) - not suspended; S15 (n = 10) - suspended for 15 days and S36 (n = 10) - suspended for 36 days. For densitometric analysis vertebrae were radiographed, scanned, digitized and analyzed by the computer program ImageJ®. There was a statistically significant increase in bone mineral density in group S15, probably by the restlessness of the animals to the suspension, with a decrease in group S36, and this hypothetically is linked to the accommodation of the rats, concluding that the tail suspension altered bone mineral density in first time with a decrease over time.

Cysteine proteinase inhibitors regulate human and mouse osteoclastogenesis by interfering with RANK signaling

The cysteine proteinase inhibitor cystatin C inhibited RANKL-stimulated osteoclast formation in mouse bone marrow macrophage cultures, an effect associated with decreased mRNA expression of Acp5, Calcr, Ctsk, Mmp9, Itgb3, and Atp6i, without effect on proliferation or apoptosis. The effects were concentration dependent with half-maximal inhibition at 0.3 μM. Cystatin C also inhibited osteoclast formation when RANKL-stimulated osteoclasts were cultured on bone, leading to decreased formation of resorption pits. RANKL-stimulated cells retained characteristics of phagocytotic macrophages when cotreated with cystatin C. Three other cysteine proteinase inhibitors, cystatin D, Z-RLVG-CHN2 (IC50 0.1 μM), and E-64 (IC 50 3 μM), also inhibited osteoclast formation in RANKL-stimulated macrophages. In addition, cystatin C, Z-RLVG-CHN2, and E-64 inhibited osteoclastic differentiation of RANKL-stimulated CD14+ human monocytes. The effect by cystatin C on differentiation of bone marrow macrophages was exerted at an early stage after RANKL stimulation and was associated with early (4 h) inhibition of c-Fos expression and decreased protein and nuclear translocation of c-Fos. Subsequently, p52, p65, IκBα, and Nfatc1 mRNA were decreased. Cystatin C was internalized in osteoclast progenitors, a process requiring RANKL stimulation. These data show that cystatin C inhibits osteoclast differentiation and formation by interfering intracellularly with signaling pathways downstream RANK. © FASEB.

Nitensidine A, a guanidine alkaloid from Pterogyne nitens, induces osteoclastic cell death

Nitensidine A is a guanidine alkaloid isolated from Pterogyne nitens, a common plant in South America. To gain insight into the biological activity of P. nitens-produced compounds, we examined herein their biological effects on osteoclasts, multinucleated giant cells that regulate bone metabolism by resorbing bone. Among four guanidine alkaloids (i.e., galegine, nitensidine A, pterogynidine, and pterogynine), nitensidine A and pterogynine exhibited anti-osteoclastic effects at 10 μM by reducing the number of osteoclasts on the culture plate whereas galegine and pterogynidine did not. The anti-osteoclastic activities of nitensidine A and pterogynine were exerted in a concentration-dependent manner, whereas nitensidine A exhibited an approximate threefold stronger effect than pterogynine (IC50 values: nitensidine A, 0.93 ± 0.024 μM; pterogynine, 2.7 ± 0.40 μM). In the present study, the anti-osteoclastic effects of two synthetic nitensidine A derivatives (nitensidine AT and AU) were also examined to gain insight into the structural features of nitensidine A that exert an anti-osteoclastic effect. The anti-osteoclastic effect of nitensidine A was greatly reduced by substituting the imino nitrogen atom in nitensidine A with sulfur or oxygen. According to the differences in chemical structures and anti-osteoclastic effects of the four guanidine alkaloids and the two synthetic nitensidine A derivatives, it is suggested that the number, binding site, and polymerization degree of isoprenyl moiety in the guanidine alkaloids and the imino nitrogen atom cooperatively contribute to their anti-osteoclastic effects. © 2013 Springer Science+Business Media Dordrecht.

The role of cytokines in inflammatory bone loss

Chronic inflammatory processes close to bone often lead to loss of bone in diseases such as rheumatoid arthritis, periodontitis, loosened joint prosthesis and tooth implants. This is mainly due to local formation of bone resorbing osteoclasts which degrade bone without any subsequent coupling to new bone formation. Crucial for osteoclastogenesis is stimulation of mononuclear osteoclast progenitors by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) which induces their differentiation along the osteoclastic lineage and the fusion to mature, multinucleated osteoclasts. M-CSF and RANKL are produced by osteoblasts/ osteocytes and by synovial and periodontal fibroblasts and the expression is regulated by pro- and anti-inflammatory cytokines. These cytokines also regulate osteoclastic differentiation by direct effects on the progenitor cells. In the present overview, we introduce the basic concepts of osteoclast progenitor cell differentiation and summarize the current knowledge on cytokines stimulating and inhibiting osteoclastogenesis by direct and indirect mechanisms. © Informa Healthcare USA, Inc.

Reação histológica do periodonto, subjacente à região de furca perfurada e preenchida com diferentes materiais, em molares de ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Densidade mineral óssea de vértebras de ratos wistar suspensos pela cauda por 15 e 36 dias

Pós-graduação em Ciência Animal - FMVA

Efeito da movimentação ortodôntica na progressão da doença periodontal induzida em ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Marcação fluorescente de cálcio em tecidos de suporte após a movimentação dentária experimental em ratos

Pós-graduação em Odontologia - FOA

Efeito da deficiência estrogênica associada ao consumo de álcool no côndilo mandibular de ratas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estudo histomorfométrico e imunoistoquímico dos efeitos da terapia fotodinâmica antimicrobiana no tratamento da doença periodontal induzida em ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)