RESUMO
Excessive osteoclast formation and bone resorption are related to osteolytic diseases. Delta drosophila homolog-like 2 (Dlk2), a member of the epidermal growth factor (EGF)-like superfamily, reportedly regulates adipocyte differentiation, but its roles in bone homeostasis are unclear. In this study, we demonstrated that Dlk2 deletion in osteoclasts significantly inhibited osteoclast formation in vitro and contributed to a high-bone-mass phenotype in vivo. Importantly, Dlk2 was shown to interact with synapse-associated protein 1 (Syap1), which regulates Akt phosphorylation at Ser473. Dlk2 deletion inhibited Syap1-mediated activation of the AktSer473, ERK1/2 and p38 signaling cascades. Additionally, Dlk2 deficiency exhibits increased bone mass in ovariectomized mice. Our results reveal the important roles of the Dlk2-Syap1 signaling pathway in osteoclast differentiation and osteoclast-related bone disorders.
Assuntos
Osteoclastos , Proteínas Proto-Oncogênicas c-akt , Animais , Camundongos , Drosophila , Homeostase , Sistema de Sinalização das MAP Quinases , Transdução de SinaisRESUMO
Artificial prosthesis is wildly used in clinical medicine for degenerative disease such as osteoclast-related diseases. However, the material wear particles released from the surface of prostheses cause prosthetic loosening as a result of aseptic osteolysis in long-term use. Therefore, it is important to find an agent that inhibits the formation and function of osteoclast for therapeutic use. Notch signaling pathway plays a lot of roles in cell proliferation, differentiation, and apoptosis. However, the role of Notch signaling pathway in osteoclastogenesis remains unclear. The aim of this study is to assess the effects of γ-secretase inhibitor DAPT on osteoclastogenesis via Notch signaling pathway in vitro and titanium particle-induced osteolysis in vivo. In animal experiments, the inhibitory effect of DAPT on titanium particle-induced osteolysis in a mouse calvaria model was demonstrated. Interestingly, few resorption pits were observed following administration of DAPT and almost no osteoclasts formed at high concentration of DAPT. in vitro experiments revealed the mechanism of the effects of DAPT on osteoclastogenesis. DAPT inhibited the formation and function of osteoclast by blocking RANKL-induced Notch2-NF-κB complex signaling pathway. In conclusion, these results indicated that DAPT could prevent and cure titanium particle-induced prosthetic loosening and other osteoclast-related diseases.
Assuntos
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Diaminas/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Osteólise/tratamento farmacológico , Osteólise/etiologia , Tiazóis/uso terapêutico , Titânio/efeitos adversos , Animais , Células Cultivadas , Diaminas/farmacologia , Inibidores Enzimáticos/farmacologia , Camundongos Endogâmicos C57BL , Osteólise/metabolismo , Próteses e Implantes/efeitos adversos , Ligante RANK/metabolismo , Receptor Notch2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tiazóis/farmacologiaRESUMO
BACKGROUND: Periodontally accelerated osteogenic orthodontics (PAOO) is a treatment for bone defects associated with a lack of bone graft stability, especially in coronal locations. This study aimed to compare a modified technique of membrane fixation that utilizes periosteal sutures (using a pouch design) with the traditional approach, which does not use membrane fixation. METHODS: Twenty-eight patients with a total of 168 teeth treated were divided into two groups: 1-A, in which patients were treated using the modified technique (with membrane fixation), and group 2-B, in which patients were treated using the traditional technique (without membrane fixation). The postoperative bone thickness was evaluated via radiographic examination. RESULTS: Postoperative improvements in bone augmentation were detected in both groups. At 12 months, the values of the CHBT (measured from the midpoint of the coronal third to the labial cortical surface, 0.84 ± 0.33 mm) and the values of VBL (measured from the alveolar crest to the cemento-enamel junction, - 2.35 ± 0.80 mm)were significantly greater in the modified technique group than those in the traditional technique group (CHBT:0.12 ± 0.21 mm and VBL:-1.39 ± 0.99 mm; P = 0.00 and P = 0.01). CONCLUSIONS: This study shows that compared to the traditional technique, the modified PAOO technique with membrane fixation using periosteal sutures provides improved graft stabilization, superior coronal augmentation and satisfactory vertical volume.
Assuntos
Processo Alveolar/cirurgia , Transplante Ósseo/métodos , Ortodontia Corretiva/métodos , Procedimentos Cirúrgicos Ortognáticos/métodos , Osteogênese/fisiologia , Osteotomia/métodos , Aumento do Rebordo Alveolar/métodos , Humanos , Ortodontia Corretiva/instrumentação , Técnicas de Movimentação Dentária/métodos , Resultado do TratamentoRESUMO
Considering the high rate of osteoclast-related diseases worldwide, research targeting osteoclast formation/function is crucial. In vitro, we demonstrated that chitooligosaccharide (CS) dramatically inhibited osteoclastogenesis as well as osteoclast function dose-dependently. CS suppressed osteoclast-specific genes expression during osteoclastogenesis. Furthermore, we found that CS attenuated receptor activator of nuclear factor kappa B ligand (RANKL)-mediated mitogen-activated protein kinase (MAPK) pathway involving p38, erk1/2, and jnk, leading to the reduced expression of c-fos and nuclear factor of activated T cells c1 (NFATc1) during osteoclast differentiation. In vivo, we found CS protected rats from periodontitis-induced alveolar bone loss by micro-computerized tomography and histological analysis. Overall, CS inhibited RANKL-induced osteoclastogenesis and ligature-induced rat periodontitis model, probably by suppressing the MAPK/c-fos/NFATc1 signaling pathway. Therefore, CS may be a safe and promising treatment for osteoclast-related diseases.
Assuntos
Quitina/análogos & derivados , Osteogênese/efeitos dos fármacos , Ligante RANK/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Quitina/farmacologia , Quitosana , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mitógenos/farmacologia , Fatores de Transcrição NFATC/metabolismo , Oligossacarídeos , Osteoclastos/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ligante RANK/metabolismo , RatosRESUMO
A series of osteolytic bone diseases are usually related to excessive bone resorption and osteoclast formation. Thus, agents or drugs which can target osteoclast development and attenuate bone loss are potentially considerable in preventing and treating of bone lytic diseases. In recent years, many studies have reported that Notch signaling has substantial impacts on the process of osteoclast differentiation, maturation, and bone destruction. In the present study, we showed that LY411575, a γ-secretase inhibitor, could potently suppress osteoclast differentiation, osteoclast-specific gene expression, and bone resorption via suppressing Notch/HES1/MAPK (ERK and p38)/Akt-mediated NFATc1 induction in vitro. Consistent with in vitro results, LY411575 exhibited protective effects in lipopolysaccharides-induced calvarial bone destruction in vivo. Collectively, these results indicate that LY411575 may have therapeutic potential in the treatment of osteoclast-mediated osteolytic bone diseases.
Assuntos
Alanina/análogos & derivados , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Azepinas/farmacologia , Inibidores Enzimáticos/farmacologia , Osteogênese/efeitos dos fármacos , Osteólise/induzido quimicamente , Osteólise/patologia , Crânio/patologia , Actinas/metabolismo , Alanina/farmacologia , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Reabsorção Óssea/complicações , Reabsorção Óssea/genética , Reabsorção Óssea/patologia , Morte Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Fusão Celular , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos , Masculino , Camundongos Endogâmicos C57BL , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteogênese/genética , Osteólise/complicações , Osteólise/genética , Podossomos/efeitos dos fármacos , Podossomos/metabolismo , Substâncias Protetoras/farmacologia , Ligante RANK/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
To evaluate the feasibility of the orthodontic traction after local resection of the condylar osteochondroma (OC).From November 2011 to September 2016, consecutive patients with condylar OC who underwent orthodontic extraction after local resection of the mass were reviewed. Clinical data and cone-beam computed tomography (CT) were obtained before treatment (T0), 1 week after surgery (T1), and at least 6-month follow-up after OC resection (T2). Repeated-measures analysis of variance with Bonferroni multiple-comparison test was used to compare the 3-dimensional cephalometric variables at different time points and the paired t test was used to compare changes of temporomandibular joint (TMJ) space between the 2 sides at T1 and T2.The sample consisted of 23 patients (16 females and 7 males). The mean postoperative follow-up interval was 10.9 months. No recurrence was observed during the postoperative follow-up period. Facial symmetry and occlusion were greatly improved. B deviation and the distance of gonion on the OC-affected side to the Frankfort horizontal (FH) were significantly improved from T0 to T1 and T2 (Pâ<â.01). The anterior space (AS) and superior space (SS) of the OC-affected side were significantly larger than that of the contralateral side at T1 in parasagittal CT views (Pâ<â.05), while no difference was found between the two sides at T2.Local resection is an effective technique with less damage to the condyle. The application of postoperative directional traction could guide the condyle into the fossa, achieve normal TMJ space and stable occlusion, and eventually provide functional and esthetic outcomes.