RESUMEN
BACKGROUND: The pathogenesis of traumatic temporomandibular joint (TMJ) bony ankylosis remains unknown. This study aimed to explore the pathogenesis of traumatic TMJ bony ankylosis in a rat model. METHODS: Twenty-four 3-week-old male Sprague-Dawley rats were used in this study. Excision of the whole disc, the fibrocartilage damage of the condyle and glenoid fossa, and narrowed joint space were performed in the left TMJ of the operation group to induce TMJ bony ankylosis (experimental side). The right TMJ underwent a sham operation (sham side). The control group did not undergo any operations. At 1, 4, and 8 weeks postoperatively, rats of the operation group were sacrificed and TMJ complexes were evaluated by gross observation, Micro-CT, histological examinations, and immunofluorescence microscopy. Total RNA of TMJ complexes in the operation group were analyzed using RNA-seq. RESULTS: Gross observations revealed TMJ bony ankylosis on the experimental side. Micro-CT analysis demonstrated that compared to the sham side, the experimental side showed a larger volume of growth, and a considerable calcified bone callus formation in the narrowed joint space and on the rougher articular surfaces. Histological examinations indicated that endochondral ossification was observed on the experimental side, but not on the sham side. RNA-seq analysis and immunofluorescence revealed that Matrix metallopeptidase 13 (MMP13) and Runt-related transcription factor 2 (RUNX2) genes of endochondral ossification were significantly more downregulated on the experimental side than on the sham side. The primary pathways related to endochondral ossification were Parathyroid hormone synthesis, secretion and action, Relaxin signaling pathway, and IL-17 signaling pathway. CONCLUSIONS: The present study provided an innovative and reliable rat model of TMJ bony ankylosis by compound trauma and narrowed joint space. Furthermore, we demonstrated the downregulation of MMP13 and RUNX2 in the process of endochondral ossification in TMJ bony ankylosis.
Asunto(s)
Anquilosis , Cóndilo Mandibular , Masculino , Ratas , Animales , Cóndilo Mandibular/diagnóstico por imagen , Cóndilo Mandibular/lesiones , Cóndilo Mandibular/cirugía , Ratas Sprague-Dawley , Anquilosis/etiología , Articulación TemporomandibularRESUMEN
OBJECTIVES: Odontogenic inflammatory diseases are main causes for alveolar bone breakdown and teeth loss, leaving great difficulties in denture restoration. Local inflammatory granulation tissue (IGT) is considered as pathological tissue and required to be removed. However, there are many evidences supporting that under appropriate intervention, IGT in alveolar bone maybe transformed into reparative granulation tissue (RGT), followed by ossification. Therefore, this study aimed to discover a specific target to promote this transformation. MATERIALS AND METHODS: After drawing out histological differences between IGT and RGT with haematoxylin and eosin (H&E) and immunohistochemical (IHC) assay staining, TMT-labelled quantitative proteomic analysis was applied to identify potential targets. RESULTS: The most striking histological property of RGT was found to be ECM deposition, which significantly decreased inflammatory cells, prominently increased fibroblasts as well as triggered changes of vascular types. Combined with histological findings and proteomic analysis, five KEGG pathways were associated with ECM, inflammation and angiogenesis and 49 pathways involved in differentially expressed proteins. COL1A1 was not only the most up-regulated protein, but also one of main hubs in protein-protein interaction regulatory network. Specific protease cathepsin K (CTSK) was identified. Level of CTSK in RGT was down-regulated to 69.10-76.97% (p < .05), with significantly up-regulated COL1A1, COL1A2, FN1 and TGFB1 included in focal adhesion, PI3K-Akt signalling pathways and angiogenesis. CTSK involved in transformation from IGT to RGT. CONCLUSIONS: CTSK might be a target to regulate transformation from IGT to RGT in alveolar bone through ECM, stem cells and angiogenesis mechanisms. However, further research is also clearly required.
Asunto(s)
Fosfatidilinositol 3-Quinasas , Proteómica , Tejido de Granulación , Humanos , Osteogénesis , Células MadreRESUMEN
OBJECTIVES: To investigate the therapeutic effect of gelatin microspheres containing different concentrations of calcitonin gene-related peptide (CGRP) or substance P on repairing bone defects in a rabbit osteoporosis model. RESULTS: Gelatin microspheres containing different concentrations of CGRP or substance P promoted osteogenesis after 3 months in a rabbit osteoporotic bone defective model. From micro-computed tomography imaging results, 10 nM CGRP was optimal for increasing the trabecular number and decreasing the trabecular bone separation degree; similar effects were observed with the microspheres containing 1 µM substance P. Histological analysis showed that the gelatin microspheres containing CGRP or substance P, regardless of the concentration, effectively promoted osteogenesis, and the highest effect was achieved in the groups containing 1 µM CGRP or 1 µM substance P. CONCLUSIONS: Gelatin microspheres containing CGRP or substance P effectively promoted osteogenesis in a rabbit osteoporotic bone defect model dose-dependently, though their effects in repairing human alveolar ridge defects still need further investigation.
Asunto(s)
Huesos/patología , Péptido Relacionado con Gen de Calcitonina/uso terapéutico , Gelatina/química , Microesferas , Osteoporosis/tratamiento farmacológico , Sustancia P/uso terapéutico , Cicatrización de Heridas , Animales , Regeneración Ósea/efectos de los fármacos , Huesos/diagnóstico por imagen , Huesos/efectos de los fármacos , Péptido Relacionado con Gen de Calcitonina/farmacología , Preparaciones de Acción Retardada , Modelos Animales de Enfermedad , Femenino , Microscopía Electrónica de Rastreo , Osteoporosis/diagnóstico por imagen , Osteoporosis/patología , Ovariectomía , Conejos , Coloración y Etiquetado , Sustancia P/farmacología , Cicatrización de Heridas/efectos de los fármacos , Microtomografía por Rayos XRESUMEN
Dentoalveolar surgery, formerly known as dental surgery or oral surgery, is one of the basic branches of oral and maxillofacial surgery. While it has a long history; however, there are great differences in its evolution globally. This article presents a brief review on the development of dentoalveolar surgery internationally. Furthermore, a systematic review on its development in China, is detailed in 6 stages. However, while its development in China since 2005 has been most profound, improvements are still needed in treatment concepts, instruments, treatment processes, attention to high-risk populations and cooperation with other dental/medical disciplines. Future projections based on present standards of care are also presented.
Asunto(s)
Procedimientos Quirúrgicos Orales/instrumentación , Cirugía Bucal/tendencias , China , Predicción , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Procedimientos Quirúrgicos Orales/historia , Cirugía Bucal/historiaRESUMEN
The rhesus macaque (Macaca mulatta) is the most widely distributed nonhuman primate species in the world, with six subspecies distributed through China. From 2012 to 2014, we conducted studies on the body mass and morphological variation of the southernmost subspecies M. m. brevicaudus in Nanwan Nature Reserve for Rhesus Macaque, Hainan, China. We compared measurements with other populations of this species. We also investigated the inter-group body mass variation from seven provisioned free-ranging groups in our study site. Our results show that M. m. brevicaudus has the smallest body size, the smallest body mass, and the shortest tail among rhesus macaque subspecies. Its sexual dimorphism score is also among the lowest, which is similar to other southern distributed subspecies in China, but smaller than northern distributed subspecies. We found that the average body mass of female macaques is not correlated with their dominance ranks. There are significant differences in body mass among the seven adjacent study groups at the same site, suggesting the existence of inter-group competition. Average body mass of a group is better described by a quadratic function of group size than a linear one as predicted by the socio-ecological model. Am. J. Primatol. 78:679-698, 2016. © 2016 Wiley Periodicals, Inc.
Asunto(s)
Macaca mulatta , Predominio Social , Distribución Animal , Animales , Tamaño Corporal , China , Femenino , MasculinoRESUMEN
BACKGROUND: The pathogenesis of traumatic TMJ ankylosis remains unclear. This study aimed to verify the role of the lateral pterygoid muscle in the pathogenesis of traumatic temporomandibular joint (TMJ) bony ankylosis. METHODS: Eight 6-month-old male sheep were used in this study. Bilateral TMJ osteotomies were performed to induce sagittal fractures of the mandibular condyle. The lateral one-fourth segment of the disc was removed to establish a model of TMJ bony ankylosis. Subsequently, the function of the left and right lateral pterygoid muscles was blocked (experimental group) or maintained (control group), respectively. At 12 weeks postoperatively, animals were sacrificed and TMJ complex samples were evaluated by gross observation, spiral computed tomography (CT), micro-CT, and histological examinations. RESULTS: Gross observation revealed bony ankylosis in the control TMJs and fibrous adhesions in the experimental TMJs. Spiral CT and micro-CT demonstrated that, compared to the experimental group, the control group showed calcified callus formation in the joint space and roughened articular surfaces after new bone formation, which protruded into the joint space. Maximum mediolateral and anteroposterior condylar diameters were significantly larger in the control group than in the experimental group. Micro-CT also showed that the primary growth orientation of new trabeculae was consistent with the direction of lateral pterygoid traction in the control group, but not in the experimental group. Histological examination showed fibro-osseous ankylosis in the control group, but not in the experimental group. CONCLUSIONS: The lateral pterygoid simulates the effects of distraction osteogenesis, which is an important factor in the pathogenesis of TMJ bony ankylosis during the healing of sagittal condylar fractures.
Asunto(s)
Anquilosis/complicaciones , Músculos Pterigoideos/patología , Trastornos de la Articulación Temporomandibular/complicaciones , Animales , Masculino , Cóndilo Mandibular , Ovinos , Articulación TemporomandibularRESUMEN
OBJECTIVE: This study was conducted to investigate the complications that occur after surgical treatment of sagittal fracture of the mandibular condyle (SFMC). METHODS: A retrospective study was conducted on patients in whom SFMC was treated using surgical methods (87 patients, 105 sides) between January 1995 and December 2011 (79 sides were treated by rigid internal fixation and the remaining 26 sides were removed the condylar fragments). The longest follow-up was 17 years, and the shortest was 2 years. Follow-ups were conducted to assess mandibular activity, mouth opening, and computed tomography scans of condylar morphologic alterations. The postoperative complications were evaluated and the causes were analyzed. RESULTS: We observed 3 patients with joint ankylosis (all of them were removed the condylar fragments); 8, mouth opening less than 30 mm; 23, deviation on mouth opening at 6 months. At 4 weeks, 19 patients had facial nerve weakness, which was resolved within 6 months. The radiological investigation showed complete remodeling in 56.2% of the condyles (in the 59 sides, 57 sides were treated by rigid internal fixation and 2 sides were removed the condylar fragments); partial remodeling 27.6% condyles (in the 29 sides, 20 sides were treated by rigid internal fixation and 9 sides were removed the condylar fragments); poor remodeling, 16.2% condyles (in the 17 sides, 2 sides were treated by rigid internal fixation and 15 sides were removed the condylar fragments). CONCLUSIONS: Surgical treatment of SFMC is not perfect. There were some complications that occurred after the surgical treatment of SFMC. The findings also indicate that condylar anatomic reduction is the basis for functional recovery and, therefore, rigid fixation should be implemented. Furthermore, the removal of condylar fragments should be performed with caution, and if used, the fragments should be removed entirely.
Asunto(s)
Fijación Interna de Fracturas/métodos , Cóndilo Mandibular/lesiones , Fracturas Mandibulares/cirugía , Adolescente , Adulto , Femenino , Humanos , Masculino , Cóndilo Mandibular/diagnóstico por imagen , Cóndilo Mandibular/cirugía , Fracturas Mandibulares/diagnóstico por imagen , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto JovenRESUMEN
To evaluate clinically and radiographically an alveolar ridge, preservation technique with deproteinized bovine bone graft and absorbable collagen membrane and then restoration with delayed implants were done. The study included 30 patients. The trial group's sockets were filled with deproteinized bovine bone graft (Bio-Oss) and covered with absorbable collagen membrane (Bio-Gide). The control group's sockets healed without any treatment. Panoramic radiograph and computed tomography were taken immediately after graft and 3 and 6 months later to evaluate the height, width, and volume change of the alveolar ridge bone. Dental implants were inserted in all sockets at 6 months, and osseointegration condition was evaluated in the following 12 months. All sockets healed uneventfully. In the trial group, the mean (SD) height reduction of the alveolar ridge bone was 1.05 (0.24) mm at 3 months and 1.54 (0.25) mm at 6 months. The width reduction was 1.11 (0.13) mm at 3 months and 1.84 (0.35) mm at 6 months. Bone volume reduction was 193.79 (21.47) mm at 3 months and 262.06 (33.08) mm at 6 months. At the same trend, in the control group, the bone height reduction was 2.12 (0.15) mm at 3 months and 3.26 (0.29) mm at 6 months. The width reduction was 2.72 (0.19) mm at 3 months and 3.56 (0.28) mm at 6 months. Bone volume reduction was 252.19 (37.21) mm at 3 months and 342.32 (36.41) mm at 6 months. There was a significant difference in alveolar ridge bone height, width, and volume reduction in the 2 groups. The osseointegration condition had no significant difference between the 2 groups. This study suggested that the deproteinized bovine bone graft and absorbable collagen membrane were beneficial to preserve the alveolar ridge bone and had no influence on the osseointegration of delayed implant.
Asunto(s)
Aumento de la Cresta Alveolar/métodos , Sustitutos de Huesos/uso terapéutico , Colágeno , Implantación Dental Endoósea/métodos , Membranas Artificiales , Minerales/uso terapéutico , Implantes Absorbibles , Adulto , Pérdida de Hueso Alveolar/clasificación , Proceso Alveolar/diagnóstico por imagen , Animales , Bovinos , Implantes Dentales , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Oseointegración/fisiología , Radiografía , Alveolo Dental/cirugía , Adulto JovenRESUMEN
OBJECTIVE: To compare the efficacies of non-surgical treatment for pediatric and adult sagittal fractures of mandibular condyle. METHODS: From January 1985 to December 2010, our department treated 67 cases (82 sides) sagittal fractures of mandibular condyle with occlusal splint at a height of 1-2 mm in molar region for six months or other non-surgical treatment. Their clinical and radiological remodeling of affected condyles after treatment were reviewed at six mouths, one year and each year after treatment. They were divided into 2 groups according to age. There were 28 patients (34 sides) aged over 12 years and 39 patients (48 sides) under 12 years. During a follow-up period of 2-25 years, mandibular activity, mouth opening and parallel CT scan of condylar morphological alterations were examined. RESULTS: Under 12-year-old group:good mandibular function was observed in 39 patients. Maximal mouth opening over 35 mm was achieved at 6 months.Only 11 of 39 patients had deviation on mouth opening at 6 months.Radiological studies showed that 32 condyles were complete remodeling and 16 condyles were partial remodeling. Poor remodeling was not observed. Over 12-year-old group:Ankylosis occurred in 4 joints. And 15 of 28 patients had deviation on mouth opening at 6 months.Radiological studies showed the remodeling of condyles was complete (n = 6), partial (n = 16) and poor (n = 12) respectively. CONCLUSION: Mandibular functional recovery and condylar remodeling are better in children with more powerful healing and reconstructing capacities.
Asunto(s)
Cóndilo Mandibular/patología , Fracturas Mandibulares/terapia , Ferulas Oclusales , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Delayed healing of diabetic cutaneous wounds is one of the most common complications of type 2 diabetes mellitus (T2DM), which can bring great distress to patients. In diabetic patients, macrophages accumulate around skin wounds and produce NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasomes, which in turn undergo pyroptosis and produce inflammatory factors such as interleukin-1ß that affect wound healing. Although our previous study revealed that apoptotic extracellular vesicles (ApoEVs) produced from mesenchymal stem cells (MSCs) improve cutaneous wound healing in normal C57BL/6 mice, whether ApoEVs can also improve diabetic wound healing remains unclear. METHODS: Umbilical cord mesenchymal stem cells (UCMSCs) were cultured in vitro and apoptosis was induced. ApoEVs were extracted and identified and used in a T2DM mouse cutaneous wound model to evaluate the efficacy. The inhibitory effect of ApoEVs on macrophage pyroptosis was verified in vivo and in vitro, and the level of oxidative stress in macrophages was assessed to explore the mechanism by which ApoEVs play a role. RESULTS: UCMSC-derived ApoEVs improved skin defect healing in T2DM mice. Moreover, UCMSC-derived ApoEVs inhibited macrophage pyroptosis in T2DM mice in vivo as well as in vitro under high-glucose culture conditions. In addition, we demonstrated that ApoEVs reduce oxidative stress levels, which is a possible mechanism by which they inhibit macrophage pyroptosis. CONCLUSIONS: Our study confirmed that local application of UCMSC-derived ApoEVs improved cutaneous wound healing in T2DM mice. ApoEVs, as products of MSC apoptosis, can inhibit macrophage pyroptosis and regulate the death process by decreasing the level of oxidative stress.
Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Vesículas Extracelulares , Células Madre Mesenquimatosas , Animales , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Piroptosis , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Experimental/terapia , Apoptosis , Modelos Animales de Enfermedad , Macrófagos , Cordón Umbilical , Cicatrización de HeridasRESUMEN
PURPOSE: To verify the efficacy and safety of calcined cattle bone grafting material in filling alveolar bone defect after tooth extraction. METHODS: A randomized, bind, parallel, positive-control multicenter clinical trial was conducted. A total of 280 subjects were randomly assigned to either the experimental group (calcined cattle bone group) or control group (Bio-Oss group) equally. The main efficacy indicator was the imaging changes 24 weeks after material implantation. Secondary efficacy indicators were wound healing, rejection, bone metabolism, post-filling symptoms and signs of bone infection. The safety of material was assessed by the incidence of adverse events and serious adverse events. SAS 8.2 software package was used for statistical analysis. RESULTS: A total of 280 cases were included, of them 267 cases completed the study while 13 cases fell off. The effective rate of FAS(PPS) was 90.58%(97.46%) in the experimental group and 87.05% (95.04%) in the control group. The difference of effective rate between the experimental group and control group (95%CI) was 3.53% (-3.88%, 10.94%) of FAS, 2.42% (-2.38%, 7.22%) of PPS, and there was no significant difference between the two groups. The incision healing of the two groups was good, and the incidence of rejection, bone infection signs, post-filling symptoms and bone metabolic changes was very low. The incidence of adverse events was similar in the two groups, and no serious adverse events related to the study materials occurred. CONCLUSIONS: The efficacy of calcined cattle bone grafting material in filling alveolar bone defect after tooth extraction is not inferior to that of Bio-Oss, and it is safe and effective for alveolar bone defect repair.
Asunto(s)
Pérdida de Hueso Alveolar , Aumento de la Cresta Alveolar , Sustitutos de Huesos , Humanos , Bovinos , Animales , Trasplante Óseo/efectos adversos , Minerales , Extracción Dental/efectos adversos , Atención Odontológica , Huesos/cirugía , Alveolo Dental/cirugía , Aumento de la Cresta Alveolar/métodos , Sustitutos de Huesos/efectos adversos , Pérdida de Hueso Alveolar/diagnóstico por imagen , Pérdida de Hueso Alveolar/cirugíaRESUMEN
PURPOSE: The aim of this retrospective study was to present the findings of an open packing method after enucleation of large keratocystic odontogenic tumors (KCOTs) in the mandible. PATIENTS AND METHODS: We performed a retrospective case series study of 27 patients with KCOTs larger than 5 cm treated at our institution between September 2003 and September 2008. A conservative surgical treatment was applied, which involved enucleation of the primary lesion and open packing of the residual osseous defect with iodoform gauze for secondary healing. Bone regeneration, tumor recurrence, and surgical complications were observed and analyzed. We used the χ(2) test and Pearson correlation coefficient for statistical analysis. RESULTS: The postoperative follow-up time was 52.3 months on average (range, 24 to 84 months). The packing gauze was changed every 2 weeks after enucleation, and the total duration for packing was 10.2 months on average (range, 7-15 months). Bone regeneration and satisfactory secondary healing were observed clinically and radiographically after treatment. Only 1 case had a recurrence 6 months after initial treatment, which was attributed to insufficient bony unroofing during enucleation. The recurrent lesion was re-treated by the same method, and no recurrence occurred in the following 6 years. No serious complications from this method of treatment were observed. No significant variables were found to be related to the recurrence. CONCLUSIONS: Enucleation with subsequent open packing was shown to be a conservative and comfortable treatment for patients and appears to be an effective choice for the management of large KCOTs in the mandible.
Asunto(s)
Antiinfecciosos Locales/uso terapéutico , Hidrocarburos Yodados/uso terapéutico , Neoplasias Mandibulares/cirugía , Tumores Odontogénicos/cirugía , Tampones Quirúrgicos , Adolescente , Adulto , Regeneración Ósea/fisiología , Niño , Legrado/métodos , Epitelio/patología , Femenino , Estudios de Seguimiento , Tejido de Granulación/patología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Osteotomía/métodos , Dimensión del Dolor , Dolor Postoperatorio/etiología , Complicaciones Posoperatorias , Radiografía Panorámica , Estudios Retrospectivos , Resultado del Tratamiento , Cicatrización de Heridas/fisiología , Adulto JovenRESUMEN
Thromboembolic diseases, which comprise venous thromboembolic diseases and arterial thromboembolic diseases, have become the number one cause of death worldwide. To prevent or treat thrombosis, patients with thromboembolic diseases need to take antithrombotic drugs, which would increase the risk of bleeding during and after surgery. Tooth extraction is the most common operation in oral and maxillofacial surgery clinics. Although patients given oral antithrombotic drugs do not need to undergo drug withdrawal, the perioperative management of such patients remains confusing to most clinicians. Moreover, the potential risk factors for bleeding warrant further study. To improve the clinicians' knowledge of perioperative management for patients subjected to tooth extractions with oral antithrombotic drugs, experts have drafted this consensus focusing on preoperative bleeding risk assessment, intraoperative operating norms, and postoperative care to summarize the points needing attention.
RESUMEN
The aim of the present study was to observe the abrasion of implant drills and postoperative reactions for the preparation of the interradicular immediate implant bed during the COVID-19 pandemic and beyond. Thirty-two implant drills were included in four groups: blank, improved surgery, traditional surgery, and control. In the improved surgery group, a dental handpiece with a surgical bur was used to decoronate the first molar and create a hole in the middle of the retained root complex, followed by the pilot drilling protocol through the hole. The remaining root complex was separated using a surgical bur and then extracted. Subsequently, the implant bed was prepared. Implant drills were used in the traditional surgery group to complete the decoronation, hole creation, and implant-drilling processes. The tooth remained intact until the implant bed was prepared. The surface roughness of the pilot drill was observed and measured. Surgery time, postoperative reactions (swelling, pain, and trismus), and fear of coronavirus disease 2019 scale (FCV-19S) were measured and recorded, respectively. Statistical analysis revealed significant difference with surface roughness among blank group (0.41 ± 0.05 µm), improved surgery group (0.37 ± 0.06 µm), traditional surgery group (0.16 ± 0.06 µm), and control group (0.26 ± 0.04 µm) (P < .001). Significant differences were revealed with surgery time between improved surgery group (5.63 ± 1.77 min) and traditional surgery group (33.63 ± 2.13 min) (P < .001). Swelling, pain, and trismus (improved group: r ≥ 0.864, P ≤ .006; traditional group: r ≥ 0.741, P ≤ .035) were positively correlated with the FCV-19S. This study proved that a new pilot drill could only be used once in traditional surgery but could be used regularly in improved surgery. Improved surgery was more effective, efficient, and economical than the traditional surgery. The higher FCV-19S, the more severe swelling, pain, and trismus.
Asunto(s)
COVID-19 , COVID-19/epidemiología , Implantación Dental Endoósea , Humanos , Diente Molar/cirugía , Dolor/cirugía , Pandemias/prevención & control , TrismoRESUMEN
The treatment of periodontitis can be very challenging due to its complex etiologies. A new pharmacologic strategy entitled "host-modulation therapy," has been introduced to improve periodontal treatment outcomes. Supposedly, a multifunctional drug with the potential for bacterial infection prevention, host-response modulation and bone healing promotion would be a promising option for periodontitis therapy, but related studies remain substantially lacking. In this study, we successfully conjugated tetracycline with odanacatib (a selective inhibitor of cathepsin K) to construct a multifunctional drug (TC-ODN). We discovered that TC-ODN could promote macrophages polarizing toward anti-inflammatory phenotype and promote osteogenesis of PDLSCs under inflammatory microenvironment. In vivo, TC-ODN could be absorbed and distributed specifically to the bone after systemic administration, and accumulation of TC-ODN increased bone mineral density in ovariectomized rats. Importantly, periodontal administration of TC-ODN could successfully promote bone healing in periodontitis rats with alveolar bone loss. The findings in our study uncovered the excellent biocompatibility and multifunction of TC-ODN, including bone-targeted accumulation, immunoregulation, anti-inflammatory activity and promotion of bone healing, which might contribute to the clinical treatment of periodontitis.
RESUMEN
Tissue engineering has become an important therapeutic method for injuries. This study aimed to generate collagen-like matrix constructed by hUCMSCs combining self-assembled polypeptide and evaluate differentiated capacity, safety and biocompatibility. Human umbilical cord tissues were isolated and used to primarily culture hUCMSCs. hUCMSCs were identified using immunofluorescence and flow cytometry. Adipogenic- and osteogenic-differentiation of hUCMSCs were evaluated using Oil-red O and Alizarin-Red staining. Self-assembling collagen peptide RAD16-I hydrogel and substance P (SP) were prepared and combined together to form RAD16-I/SP complex. Surface morphology and ultrastructures were observed with scanning electron microscopic (SEM). hUCMSCs in simulated collagen-like matrix environment were plane-cultured and stereo-cultured. Cell viability was examined using CCK-8 and fluorescent staining assay. Osteogenic genes were detected with qRT-PCR and western blot assay. HE staining and Masson staining were used to assess production of mineralized nodules and collagen-like fibers, respectively. Collagen-like matrix complex by combining RAD16-I/SP complex with stereo-cultured hUCMSCs was successfully generated. hUCMSCs in collagen-like matrix complex demonstrated adipogenic-differentiation and osteogenic-differentiation potential. SP-induced RAD16-I mediated stereo-culture of hUCMSCs demonstrated higher cell activity and proliferation potential. SP-induced RAD16-I mediated stereo-culture of hUCMSCs promoted osteogenesis-related molecules expression. SP-induced RAD16-I mediated stereo-culture of hUCMSCs promoted production of mineralized nodules and triggered formation of collagen-like fibers. Cell-collagen-like matrix complex injection (RAD16-I/SP/hUCMSCs complex) exhibited better biocompatibility and no cytotoxicity. In conclusion, SP-induced RAD16-I mediated stereo-culture of hUCMSCs remarkably promoted osteogenesis-related gene expression, triggered production of mineralized nodules and formation of collagen-like fibers. This established cell-collagen-like matrix complex (RAD16-I/SP/hUCMSCs) injection exhibited better biocompatibility, without cytotoxicity.
RESUMEN
OBJECTIVES: To clarify the possible role and mechanism of Cathepsin K (CTSK) in alveolar bone regeneration mediated by jaw bone marrow mesenchymal stem cells (JBMMSC). MATERIALS AND METHODS: Tooth extraction models of Ctsk knockout mice (Ctsk-/- ) and their wildtype (WT) littermates were used to investigate the effect of CTSK on alveolar bone regeneration. The influences of deletion or inhibition of CTSK by odanacatib (ODN) on proliferation and osteogenic differentiation of JBMMSC were assessed by CCK-8, Western blot and alizarin red staining. To explore the differently expressed genes, RNA from WT and Ctsk-/- JBMMSC was sent to RNA-seq. ECAR, glucose consumption and lactate production were measured to identify the effect of Ctsk deficiency or inhibition on glycolysis. At last, we explored whether Ctsk deficiency or inhibition promoted JBMMSC proliferation and osteogenic differentiation through glycolysis. RESULTS: We found out that Ctsk knockout could promote alveolar bone regeneration in vivo. In vitro, we confirmed that both Ctsk knockout and inhibition by ODN could promote proliferation of JBMMSC, up-regulate expression of Runx2 and ALP, and enhance matrix mineralization. RNA-seq results showed that coding genes of key enzymes in glycolysis were significantly up-regulated in Ctsk-/- JBMMSC, and Ctsk deficiency or inhibition could promote glycolysis in JBMMSC. After blocking glycolysis by 3PO, the effect of Ctsk deficiency or inhibition on JBMMSC's regeneration was blocked subsequently. CONCLUSIONS: Our findings revealed that Ctsk knockout or inhibition could promote alveolar bone regeneration by enhancing JBMMSC regeneration via glycolysis. These results shed new lights on the regulatory mechanism of CTSK on bone regeneration.
Asunto(s)
Regeneración Ósea , Catepsina K/genética , Diferenciación Celular , Proliferación Celular , Células Madre Mesenquimatosas/metabolismo , Animales , Células de la Médula Ósea/citología , Catepsina K/deficiencia , Células Cultivadas , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Glucosa/metabolismo , Glucólisis , Maxilares/citología , Células Madre Mesenquimatosas/citología , Ratones , Ratones Noqueados , Osteoblastos/citología , Osteoblastos/metabolismo , OsteogénesisRESUMEN
Bone defect is a common problem and inducing osteoblasts differentiation is the key process for the regenerative repair. Recently, the mesoporous silica (MS) coated nanohydroxyapatite (nHA) particles (nHA-MS) has shown enhanced intrinsic potency for bone regeneration, whereas whether the osteogenesis potency can be further enhanced after drug delivery has not been investigated. In this study, the nHA-MS was fabricated by a novel biphase stratification growth way. The cytotoxicity in MC3T3-E1 was validated by MTT assay, apoptosis analysis and cell cycle examination. The cell uptake was observed by confocal laser scanning microscope and transmission electron microscope respectively. After adsorption with dexamethasone (DEX), the osteogenic differentiation was determined bothin vitroandin vivo. The synthesized nHA-MS showed a core-shell structure that the nanorod-like nHA was coated by a porous MS shell (â¼5 nm pores diameter, â¼50 nm thickness). A dose-dependent cytotoxicity was observed and below 10 µg ml-1was a safe concentration. The nHA-MS also showed efficient cell uptake efficiency and more efficient in DEX loading and release. After DEX adsorption, the nanoparticles exhibited enhanced osteogenic induction in MC3T3-E1 and rat calvarial bone defect regeneration. In conclusion, the nHA-MS is a favorable platform for drug delivery to obtain more enhanced osteogenesis capabilities.
Asunto(s)
Durapatita , Osteogénesis , Animales , Regeneración Ósea , Diferenciación Celular , Dexametasona/química , Durapatita/química , Ratas , Dióxido de SilicioRESUMEN
OBJECTIVES: To evaluate the therapeutic outcome of ultrasound-guided intralesional injection of bleomycin A5 on treatment of venous malformation (VM) in cervical-facial region. METHODS: Seventy-five patients (32 male, 43 female), ranging in age from 13 to 60 years old, suffering from VM in cervical-facial region were admitted to and treated at our hospital between June 2006 and February 2007. Of all the patients, 54 malformations were located in the facial region, eight in the submental region, 10 in the submandible region, and three in the cervical region; all were treated by ultrasound-guided intralesional injections of bleomycin A5. The size of the lesions ranged from 6 x 9 mm to 32 x 39 mm. Injection of bleomycin A5 on venous malformation was then carried out through the inspection of ultrasonography. Repeated course of bleomycin A5 injection was administrated for larger malformations. The amount was 8 mg each time. The therapeutic interval was two to four weeks. The therapeutic outcome on venous malformation was evaluated by physical examination and ultrasonography with Doppler according to the Shou standards, including four grades; cured, basically cured, improved, and invalid. The complications were also observed during and after injection. RESULTS: The duration of follow-up ranged from 6 to 24 months. The average times of treatment were 1.64 times. Among them, 42 patients (56%) received only one time of treatment, 21 (28%) patients received two times, nine (12%) patients received three times, and three (4%) patients received four times. According to criteria of therapeutic outcome, the results showed cured in 63 patients (84%), basically cured in 10 patients (13.33%), improved in two patients (2.67%), and none ineffective. Seventy-one patients (94.67%) had local swelling in injection region for several days and two patients (2.67%) developed temporary dizziness after treatment. There were no other complications recorded. CONCLUSIONS: Intralesional injection of bleomycin A5 establishes a promisingly effect way for patients suffering from VM in the cervical-facial region under ultrasound guidance.
Asunto(s)
Bleomicina/análogos & derivados , Fármacos Cardiovasculares/administración & dosificación , Ultrasonografía Intervencional , Malformaciones Vasculares/tratamiento farmacológico , Adolescente , Adulto , Dorso , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Fármacos Cardiovasculares/efectos adversos , China , Esquema de Medicación , Cara , Femenino , Humanos , Inyecciones Intralesiones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Malformaciones Vasculares/diagnóstico por imagen , Venas/anomalías , Venas/diagnóstico por imagen , Adulto JovenRESUMEN
PURPOSE: To investigate the incidence and the local factors of impacted permanent teeth, except for the third molar, in Chinese patients through an x-ray study. MATERIALS AND METHODS: A total of 548 impacted permanent teeth from panoramic radiographs were studied and recorded according to the patients' gender and age, tooth position, and classification of impaction. The local factors contributing to impacted permanent tooth were also investigated. RESULTS: The incidence of impacted permanent teeth in the Chinese was 6.15%. The impacted tooth showed a predilection for women and was more common in the maxilla. The impaction of the canine had the greatest occurrence, 28.10% of all impacted teeth. Vertical impaction was most common (49.09%). The chief local factor for impacted teeth was the lack of interdental space (49.64%). CONCLUSIONS: All permanent teeth can occur with impaction in Chinese patients. Dentists should perform a thorough evaluation before planning suitable treatment.