949 resultados para bone morphogenetic protein 15
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Pós-graduação em Zootecnia - FCAV
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Pós-graduação em Zootecnia - FCAV
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Pós-graduação em Zootecnia - FCAV
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The aim of this study was to use the finite element method to evaluate the distribution of stresses and strains on the local bone tissue adjacent to the miniplate used for anchorage of orthodontic forces. Methods: A 3-dimensional model composed of a hemimandible and teeth was constructed using dental computed tomographic images, in which we assembled a miniplate with fixation screws. The uprighting and mesial movements of the mandibular second molar that was anchored with the miniplate were simulated. The miniplate was loaded with horizontal forces of 2, 5, and 15 N. A moment of 11.77 N.mm was also applied. The stress and strain distributions were analyzed, and their correlations with the bone remodeling criteria and miniplate stability were assessed. Results: When orthodontic loads were applied, peak bone strain remained within the range of bone homeostasis (100-1500 mu m strain) with a balance between bone formation and resorption. The maximum deformation was found to be 1035 mu m strain with a force of 5 N. At a force of 15 N, bone resorption was observed in the region of the screws. Conclusions: We observed more stress concentration around the screws than in the cancellous bone. The levels of stress and strain increased when the force was increased but remained within physiologic levels. The anchorage system of miniplate and screws could withstand the orthodontic forces, which did not affect the stability of the miniplate.
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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.
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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.
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The myeloid differentiation factor 88 (MyD88) plays a pivotal role in Toll-like receptor (TLR)- and interleukin-1 receptor (IL-1R)-induced osteoclastogenesis. We examined the role of MyD88 on p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) activation and nucleotide-binding oligomerization domain (Nod) induction by lipopolysaccharide (LPS) and IL-1 beta, and their effect on receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) production in bone marrow stromal cell (BMSC). RANKL, Nod1, Nod2, NF-κB, and p38 protein levels were determined by Western blot. Nod2 was stimulated with muramyl dipeptide (MDP) prior to TLR4 stimulation with LPS. MyD88 deficiency markedly inhibited RANKL expression after LPS stimulation and increased OPG messenger RNA (mRNA) production. Also, MyD88 was necessary for NF-κB and p38 MAPK activation. MDP alone did not induce RANKL and OPG expressions; however, when combined with LPS, their expressions were significantly increased (p < 0.05). Our results support that MyD88 signaling has a pivotal role in osteoclastogenesis thought NF-κB and p38 activation. Nod2 and especially Nod1 levels were influenced by MyD88.
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This study aimed to evaluate the potential of bacterial cellulose-hydroxyapatite (BC-HA) composites associated with osteogenic growth peptide (OGP) or pentapeptide OGP(10–14) in bone regeneration in critical-size calvarial defects in mice. In this study, the BC-HA, BC-HA-OGP, and BC-HA-OGP(10–14) membranes were analyzed at 3, 7, 15, 30, 60, and 90 days. In each period, the specimens were evaluated by micro-computed tomography (µCT), descriptive histology, gene expression of bone biomarkers by qPCR and VEGFR-2 (vascular endothelial growth factor) quantification by ELISA. Three days post-operative, Runx2, Tnfrsf11b and Bglap bone biomarkers were upregulated mainly by BC-HA OGP and BC-HA OGP(10–14) membranes, suggesting an acceleration of the osteoblast differentiation/activity with the use of these biomaterials. At 60 and 90 days, a high percentage of bone formation was observed by µCT for BC-HA and BC-HA OGP(10–14) membranes. High expression of some bone biomarkers, such as Alpl, Spp1, and Tnfrsf11b, was also observed for the same membranes on days 60 and 90. In conclusion, the BC-HA membrane promoted a better bone formation in critical-size mice calvarial defects. Nevertheless, incorporation of the peptides at the concentration of 10−9 mol L−1 did not improve bone regeneration potential in the long-term.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)