Periodontal disease-associated compensatory expression of osteoprotegerin is lost in type 1 diabetes mellitus and correlates with alveolar bone destruction by regulating osteoclastogenesis

Alveolar bone resorption results from the inflammatory response to periodontal pathogens. Systemic diseases that affect the host response, such as type 1 diabetes mellitus (DM1), can potentiate the severity of periodontal disease (PD) and accelerate bone resorption. However, the biological mechanisms by which DM1 modulates PD are not fully understood. The aim of this study was to determine the influence of DM1 on alveolar bone resorption and to evaluate the role of receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin (OPG) in osteoclastogenesis in rats. PD was induced by means of ligature in nondiabetic and in streptozotocyn-induced DM1 rats. Morphological and morphometric analyses, stereology and osteoclast counting were performed. RANKL and OPG mRNA levels, protein content, and location were determined. PD caused alveolar bone resorption, increased the number of osteoclasts in the alveolar bone crest and also promoted changes in RANKL/OPG mRNA expression. DM1 alone showed alveolar bone destruction and an increased number of osteoclasts at the periapical and furcal regions. DM1 exacerbated these characteristics, with a greater impact on bone structure, resulting in a low OPG content and a higher RANKL/OPG ratio, which correlated with prominent osteoclastogenesis. This work demonstrates that the effects of PD and DM1 enhance bone destruction, confirms the importance of the RANKL signaling pathway in bone destruction in DM1 in animal models and suggests the existence of alternative mechanisms potentiating bone degradation in PD.

Anti-inflammatory effect of MAPK phosphatase-1 local gene transfer in inflammatory bone loss

Alveolar bone loss associated with periodontal diseases is the result of osteoclastogenesis induced by bacterial pathogens. The mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) is a critical negative regulator of immune response as a key phosphatase capable of dephosphorylating activated MAPKs. In this study, rat macrophages transduced with recombinant adenovirus (Ad.)MKP-1 specifically dephosphorylated activated MAPKs induced by lipopolysaccharide (LPS) compared with control cells. Bone marrow macrophages from MKP-1 knockout (KO) mice exhibited higher interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, and select chemokine compared with wild-type (WT) mice when stimulated by LPS. In addition, bone marrow cultures from MKP-1 KO mice exhibited significantly more osteoclastogenesis induced by LPS than when compared with WT mice. Importantly, MKP-1 gene transfer in bone marrow cells of MKP-1 KO mice significantly decreased IL-6, IL-10, TNF-α and chemokine levels, and formed fewer osteoclasts induced by LPS than compared with control group of cells. Furthermore, MKP-1 gene transfer in an experimental periodontal disease model attenuated bone resorption induced by LPS. Histological analysis confirmed that periodontal tissues transduced with Ad. MKP-1 exhibited less infiltrated inflammatory cells, less osteoclasts and less IL-6 than compared with rats of control groups. These studies indicate that MKP-1 is a key therapeutic target to control of inflammation-induced bone loss.

Treatment of periodontal disease with an Er,Cr:YSGG laser in rats exposed to cigarette smoke inhalation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Análise histomorfométrica da influência do Alendronato sódico no processo de reparo ósseo em tíbia de ratas submetidas a ovariectomia

The sodium alendronate (AS), considered as inhibitor in the osteoclasts- mediated bone resorption, promotes final effect of inhibition of resorption and increases bone mass. The objective of this research was to assess, by histomorphometry, the effect of sodium alendronate in repair bone of ovariectomized rats, in which there was performed a bone defect in the right tibia. The treated rats received a subcutaneous injection of sodic alendronate once a week, at 0.7 mg / kg, diluted with saline solution; the controls received the same volume of saline solution. In the periods of 16, 30 and 44 days after the first dose of AS, the animals were sacrificed, the right tibia was removed and processed for histomorphometric analysis. Four non-serial fields were used for the density volume quantification utilizing an integrative eyepiece with 25 points, totalizing 100 points per animal. Based on the results, the present study concludes that the ovariectomy induced osteoporosis and that the AS stimulated the bone formation. In addition, the ovariectomy decreased the estrogen levels. However, this procedure did not significantly influence the action of sodic alendronate.

Atividade de enzimas relacionadas ao processo de ossificação em girinos de Lithobates catesbeianus

Pós-graduação em Biotecnologia - IQ

Effects of oestrogen deficiency and 17 beta-estradiol therapy on bone healing in calvarial critical size defects treated with bovine bone graft

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Androgen receptors and experimental bone loss - an in vivo and in vitro study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Biology of bone tissue: structure, function, and factors that influence bone cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Porphyromonas gingivalis stimulates bone resorption by enhancing RANKL (Receptor Activator of NF-κB Ligand) through activation of toll-like receptor 2 in osteoblasts

Periodontitis has been associated with rheumatoid arthritis. In experimental arthritis, concomitant periodontitis caused by oral infection with Porphyromonas gingivalis enhances articular bone loss. The aim of this study was to investigate how lipopolysaccharide (LPS) from P. gingivalis stimulates bone resorption. The effects by LPS P. gingivalis and four other TLR2 ligands on bone resorption, osteoclast formation, and gene expression in wild type and Tlr2-deficient mice were assessed in ex vivo cultures of mouse parietal bones and in an in vivo model in which TLR2 agonists were injected subcutaneously over the skull bones. LPS P. gingivalis stimulated mineral release and matrix degradation in the parietal bone organ cultures by increasing differentiation and formation of mature osteoclasts, a response dependent on increased RANKL (receptor activator of NF-κB ligand). LPS P. gingivalis stimulated RANKL in parietal osteoblasts dependent on the presence of TLR2 and through a MyD88 and NF-κB-mediated mechanism. Similarly, the TLR2 agonists HKLM, FSL1, Pam2, and Pam3 stimulated RANKL in osteoblasts and parietal bone resorption. LPS P. gingivalis and Pam2 robustly enhanced osteoclast formation in periosteal/endosteal cell cultures by increasing RANKL. LPS P. gingivalis and Pam2 also up-regulated RANKL and osteoclastic genes in vivo, resulting in an increased number of periosteal osteoclasts and immense bone loss in wild type mice but not in Tlr2-deficient mice. These data demonstrate that LPS P. gingivalis stimulates periosteal osteoclast formation and bone resorption by stimulating RANKL in osteoblasts via TLR2. This effect might be important for periodontal bone loss and for the enhanced bone loss seen in rheumatoid arthritis patients with concomitant periodontal disease.

Efeito da suplementação com boro no metabolismo ósseo de camundongos diabéticos não obesos

Pós-graduação em Alimentos e Nutrição - FCFAR

Treatment of experimental periodontal disease by antimicrobial photodynamic therapy in nicotine-modified rats

Background The aim of this study was to compare antimicrobial photodynamic therapy (aPDT) as an adjunctive treatment to scaling and root planing (SRP) for induced periodontitis in nicotine-modified rats. Material & Methods A total of 240 rats were evenly divided into two groups: C – saline solution treatment; N – nicotine treatment. Periodontal disease was induced in both groups at the first mandibular molar. After 7 days, the ligature was removed. All animals were submitted to SRP and were divided according to the following treatments: SRP – irrigation with saline solution; Toluidine Blue-O (TBO) – irrigation with phenothiazinium dye (100 μg/ml); LLLT – laser irradiation (660 nm; 0.03 W; 4 J); and aPDT – TBO and laser irradiation. Ten animals in each group/treatment were euthanized at 7, 15 and 30 days. The histometric and immunohistochemical values were statistically analysed. Results Intragroup analysis demonstrated that in both groups the aPDT treatment resulted in lower bone loss (BL) when compared to SRP in all experimental periods. Intergroup analysis demonstrated that aPDT treatment resulted in lower BL in Group N than in Group C treated with SRP in all experimental periods. Conclusion Antimicrobial photodynamic therapy was an effective adjunctive treatment to SRP for induced periodontitis in nicotine-modified rats.

Estudo do processo de reparo de enxerto ósseo em bloco submetido ao recobrimento com etil-cianoacrilato: análise histométrica e imunoistoquímica em ratos

Pós-graduação em Odontologia - FOA

Influência da hipertensão arterial no padrão fenotípico da lesão periapical, na diferenciação dos osteoclastos, na resposta teciduale na capacidade de mineralização do cimento reparador MTA

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Modulação da doença periodontal por curcumin modificado quimicamente. Estudo de dose-resposta em roedor

Pós-graduação em Odontologia - FOAR

Patofisiologia de osteonecrose induzida por bisfosfonatos e inibidores de RANK-L

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)