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This study investigated the expression of sortilin 1 (SORT1) in cultured human dental pulp-derived stem cells (hDPSCs) and its role in their odontoblastic differentiation. Permanent teeth were extracted from five patients, and the dental pulp was harvested for explant culture. Fluorescence-activated cell sorting was used to analyze the outgrowth of adherent cells and cells that had migrated from the tissue margin. SORT1 expression was detected in hDPSCs simultaneously expressing the mesenchymal stem cell markers CD44 and CD90. The odontoblastic differentiation potential of SORT1-positive hDPSCs was examined via staining for alkaline phosphatase (ALP), an early odontoblastic differentiation marker. ALP staining was more intense in SORT1-positive than in SORT1-negative hDPSCs. Consistently, the expression of mRNA encoding SORT1 and p75NTR, a binding partner of SORT1, increased in SORT1-positive hDPSCs during odontoblastic differentiation. In addition, pro-nerve growth factor (NGF), a ligand for SORT1-p75NTR co-receptor, promoted ALP expression in SORT1-positive hDPSCs, and the interaction between SORT1 and p75NTR was detected using a coimmunoprecipitation assay. The function of SORT1 in odontoblastic differentiation was examined via RNA interference using shRNA targeting SORT1. ALP staining intensity in SORT1/shRNA-transfected cells was markedly lower than in control/shRNA-transfected cells. SORT1 knockdown decreased JUN phosphorylation and recruitment of phosphorylated JUN to the ALP promoter. Collectively, these results indicate that SORT1 is involved in the odontoblastic differentiation of hDPSCs through the JUN N-terminal kinases (JNK)/JUN signaling pathway and that the binding of SORT1 and p75NTR plays an important role in this process.
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Polpa Dentária , Odontoblastos , Humanos , Odontoblastos/metabolismo , Células-Tronco , RNA Interferente Pequeno/farmacologia , Diferenciação Celular/genética , Células CultivadasRESUMO
This study explored the relationship between the morphological characteristics of the first tarsometatarsal ligaments and fibularis longus (FL) and the severity of articular cartilage degeneration in the first tarsometatarsal joint. Sixty legs from 30 cadavers were examined. The plantar, dorsal, and medial first tarsometatarsal ligaments were classified by fiber bundle number, and their morphological characteristics (fiber bundle length, width, thickness) were measured. The FL was categorized by its continuity with the plantar first tarsometatarsal ligament (PTML): Type A, connection with the PTML only on the first metatarsal; Type B, connection along the entire PTML; and Type C, no connection with the PTML. The severity of articular cartilage degeneration was assessed in four stages. No significant differences in cartilage degeneration among ligament types were found. Negative correlations were observed between the fiber bundle width and thickness of the PTML and the severity of cartilage degeneration. FL was classified as Type A in 68%, Type B in 27%, and Type C in 5% of feet. The fiber bundle thickness of the PTML in Type B was greater than in other types. Our findings suggest that smaller fiber bundle width and thickness in the PTML may be associated with severe cartilage degeneration. The FL had continuity with the PTML in 95% of feet and could enhance the mechanical strength of the PTML in Type B feet.
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PURPOSE: In this article, we report a case of an atypical inferior gluteal artery that passed through the piriformis muscle when it emerged from the pelvic cavity in an elderly Japanese female cadaver. We speculate that this atypical artery could be entrapped and compressed by the piriformis muscle and may therefore be associated with piriformis syndrome; however, the anatomical characteristics of such an atypical artery have not been previously reported. To assess this potential association, the atypical inferior gluteal artery was anatomically examined. METHODS: The cadaver examined in this report was a 97-year-old Japanese female who was donated to The Nippon Dental University for use in medical education and research. The atypical inferior gluteal artery and surrounding structures in half of the pelvis were examined macroscopically. RESULTS: The atypical inferior gluteal artery arose from the common arterial trunk, formed by itself and the superior gluteal artery, passed through the superior proximal part of the piriformis muscle, and left the pelvic cavity. It supplies branches to the lower half of the gluteus maximus and proximal part of the long head of the biceps femoris muscle. The piriformis muscle originates from the 2nd to 4th sacral vertebrae and attaches to the greater trochanter via a single short tendon. CONCLUSION: According to our findings, when the atypical inferior gluteal artery is entrapped and compressed, ischemic signs and symptoms may emerge in the lower buttocks and proximal posterior thigh. These results provide a new perspective for the diagnosis and treatment of piriformis syndrome.
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Síndrome do Músculo Piriforme , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Coxa da Perna , Músculo Esquelético , Artérias , Nádegas/irrigação sanguínea , Pelve , CadáverRESUMO
BACKGROUND: The purpose of this study was to clarify the attachment types of the tibialis anterior tendon (TAT) in Japanese fixed cadavers and to determine the attachment site area in three dimensions. METHODS: We examined 100 feet from 50 Japanese cadavers. The TAT was classified according to differences in the number of fiber bundles as: Type I, with one fiber bundle; Type II, with two fiber bundles; and Type III, with three fiber bundles. The attachment site area of the TAT was measured using a three-dimensional scanner. RESULTS: Cases were Type II in 95% and Type III in 5%, with no cases of Type I identified. In Type II, mean attachment site areas were 85.2 ± 18.2 mm2 for the medial cuneiform bone (MCB) and 72.4 ± 19.0 mm2 for the first metatarsal bone (1 MB), showing a significantly larger area for MCB than for 1 MB. CONCLUSIONS: These findings suggest the possibility of ethnic differences in TAT attachment types and suggest that TAT attachments in Japanese individuals are highly likely to be Type II, with rare cases of Type III. Accurate measurement of attachment site areas is possible with appropriate three-dimensional measurements.
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Músculo Esquelético , Tendões , Humanos , Tornozelo , Pé , CadáverRESUMO
The lingual nerve carries somatosensory fibers from the anterior two-thirds of tongue. The parasympathetic preganglionic fibers arising from the chorda tympani also travel with the lingual nerve in the infratemporal fossa to synapse in the submandibular ganglion to innervate the sublingual gland. However, only a few studies have investigated the specific nerve that innervates the sublingual gland and surrounding tissue i.e., the so-called sublingual nerve. Therefore, this study aimed to clarify the anatomy and definition of the sublingual nerves. Thirty sides from formalin fixed cadaveric hemiheads underwent microsurgical dissection of the sublingual nerves. The sublingual nerves were found on all sides and categorized into three branches, i.e., branches to the sublingual gland, branches to the mucosa of the floor of the mouth, and gingival branches. Additionally, branches to the sublingual gland were subcategorized into types I and II based on the origin of the sublingual nerve. We suggest that the lingual nerve branches should be categorized into five branches, i.e., branches to the isthmus of the fauces, sublingual nerves, lingual branches, posterior branch to the submandibular ganglion, and branches to the sublingual ganglion.
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Nervo Lingual , Língua , Humanos , Nervo Lingual/anatomia & histologia , Língua/inervaçãoRESUMO
The 75 kDa transmembrane protein, p75(NTR), is a marker of mesenchymal stem cells (MSCs). Isolated MSCs are capable of differentiating into osteoblasts, but the molecular function of p75(NTR) in MSCs and osteoblasts is poorly understood. The aim of this study was to examine the function of p75(NTR) in the human MG63 osteoblast cell line compared to the murine MC3T3E-1 pre-osteoblast cell line. MG63 cells and MC3T3-E1 cells expressing exogenous p75(NTR) protein (denoted as p75-MG63 and p75GFP-E1, respectively) were generated to compare osteogenic differentiation and cell proliferation abilities. Overexpression of p75(NTR) induced alkaline phosphatase activity and the mRNA expression of osteoblast-related genes such as osterix and bone sialoprotein in both p75-MG63 and p75GFP-E1. Interestingly, exogenous p75(NTR) stimulated cell proliferation and cell cycle progression in p75GFP-E1, but not in p75-MG63. To elucidate any different effects of p75(NTR) expression on osteogenic differentiation and cell proliferation, we examined the mRNA expression of tropomyosin receptor kinase (trk) genes (trkA, trkB, trkC) and Nogo receptor (NgR), which are binding partners of p75(NTR). Although trkA, trkB, and trkC were detected in both p75-MG63 and p75GFP-E1, only NgR was detected in p75-MG63. We then used the K252a inhibitor of the trks to identify the signaling pathway for osteogenic differentiation and cell proliferation. Inhibition of trks by K252a suppressed p75(NTR)-mediated osteogenic differentiation of p75GFP-E1, whereas deletion of the GDI domain in P75(NTR) from the p75-MG63 produced enhanced cell proliferation compared to p75-MG63. These results suggest that p75(NTR) signaling associated with trk receptors promotes both cell proliferation and osteoblast differentiation, but that p75(NTR)-mediated proliferation may be suppressed by signaling from the p75(NTR)/NgR complex.
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Proliferação de Células , Osteoblastos/metabolismo , Receptor de Fator de Crescimento Neural/metabolismo , Fosfatase Alcalina/metabolismo , Carbazóis/farmacologia , Linhagem Celular , Humanos , Alcaloides Indólicos/farmacologia , Osteoblastos/citologia , Osteogênese , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/metabolismo , Receptor de Fator de Crescimento Neural/genética , Sialoglicoproteínas/genética , Sialoglicoproteínas/metabolismo , Transdução de Sinais , Fator de Transcrição Sp7 , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
PURPOSE: Bacterial cells in mature dental plaque produce a high concentration of short-chain fatty acids (SCFAs) such as butyrate and propionate. SCFA-treatment on human gingival epithelial Ca9-22 cells induced cell death. However, the exact mechanism underlying cell death remains unclear. In this study, the relationship between reactive oxygen species (ROS) and autophagy induction during SCFA-induced cell death was examined. METHODS: Human gingival epithelial Ca9-22 cells were treated with butyrate or propionate to induce cell death and the number of dead cells were measured using SYTOX-green dye. A siRNA for ATG5 and N-acetylcysteine (NAC) were used for autophagy reduction and ROS-scavenging, respectively. Release of damage-associated molecular patterns (DAMPs) such as Sin3A-associated protein 130 (SAP130) and high-mobility group box 1 (HMGB1) were detected using western blot. RESULTS: Reducing autophagy significantly suppressed SCFA-induced Ca9-22 cell death. ROS generation was observed upon SCFA treatment, and scavenging ROS with NAC decreased cell death. NAC also reduced the SCFA-induced increase in microtubule-associated protein 1 light chain 3B (LC3B)-I and LC3B-II, and mitigated the release of DAMPs. CONCLUSION: The findings suggest that ROS generation is necessary for autophagy, which is required for SCFA-induced cell death and accompanying DAMP release.
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Butiratos , Propionatos , Humanos , Butiratos/farmacologia , Propionatos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Ácidos Graxos Voláteis/farmacologia , Autofagia/fisiologiaRESUMO
This study aimed to elucidate the relationship between joint structures of the first tarsometatarsal and articular facet degeneration. A total of 100 feet from 50 cadavers were examined. The articular facets of the first metatarsal and medial cuneiform were categorized into four types based on the superior and inferior facets' separation, and the formation of the inferior lateral facet on the lateral plantar prominence: Type I, a single facet with no separation or inferior lateral facet; Type II-a, two facets with separation but no inferior lateral facet; Type II-b, two facets, no separation, but with an inferior lateral facet; Type III, three facets with separation and an inferior lateral facet. When both bone types matched, they were defined as Type I, Type II-a, Type II-b, and Type III joints, respectively; unmatched types were classified as Unpair joints. The severity of articular cartilage degeneration on both bones was assessed using a 5-point scale. The degeneration grade was compared among joint types. Type III joints exhibited significantly milder articular cartilage degeneration in medial cuneiform compared to Type II-a, II-b, Unpair joints. The formation of inferior lateral facet and separation of the superior and inferior facets might be crucial for the joint's stability.
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Cadáver , Humanos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Cartilagem Articular/patologia , Ossos do Metatarso/patologia , Ossos do Metatarso/anatomia & histologia , Articulações Tarsianas/patologia , Articulações Tarsianas/anatomia & histologia , Articulações do Pé/patologiaRESUMO
Non-alcoholic steatohepatitis (NASH), caused by fat buildup, can lead to liver inflammation and damage. Elucidation of the spatial distribution of fibrotic tissue in the fatty liver in NASH can be immensely useful to understand its pathogenesis. Thus, we developed a novel serial section-3D (SS3D) technique that combines high-resolution image acquisition with 3D construction software, which enabled highly detailed analysis of the mouse liver and extraction and quantification of stained tissues. Moreover, we studied the underexplored mechanism of fibrosis progression in the fatty liver in NASH by subjecting the mice to a high-fat diet (HFD), followed by lipopolysaccharide (LPS) administration. The HFD/LPS (+) group showed extensive fibrosis compared with control; additionally, the area of these fibrotic regions in the HFD/LPS (+) group was almost double that of control using our SS3D technique. LPS administration led to an increase in Tnfα and Il1ß mRNA expression and the number of macrophages in the liver. On the other hand, transforming growth factor-ß1 (Tgfß1) mRNA increased in HFD group compared to that of control group without LPS-administration. In addition, COL1A1 levels increased in hepatic stellate cell (HSC)-like XL-2 cells when treated with recombinant TGF-ß1, which attenuated with recombinant latency-associated protein (rLAP). This attenuation was rescued with LPS-activated macrophages. Therefore, we demonstrated that fatty liver produced "latent-form" of TGF-ß1, which activated by macrophages via inflammatory cytokines such as TNFα and IL1ß, resulting in activation of HSCs leading to the production of COL1A1. Moreover, we established the effectiveness of our SS3D technique in creating 3D images of fibrotic tissue, which can be used to study other diseases as well.
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Dieta Hiperlipídica , Lipopolissacarídeos , Cirrose Hepática , Macrófagos , Hepatopatia Gordurosa não Alcoólica , Fator de Crescimento Transformador beta1 , Animais , Fator de Crescimento Transformador beta1/metabolismo , Camundongos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Cirrose Hepática/patologia , Cirrose Hepática/metabolismo , Dieta Hiperlipídica/efeitos adversos , Masculino , Fígado/metabolismo , Fígado/patologia , Camundongos Endogâmicos C57BL , Ativação de Macrófagos , Imageamento Tridimensional/métodos , Modelos Animais de Doenças , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Interleucina-1beta/metabolismoRESUMO
This study aimed to clarify the relationship between the joint and ligament structures of the subtalar joint and degeneration of the subtalar articular facet. We examined 50 feet from 25 Japanese cadavers. The number of articular facets, joint congruence, and intersecting angles were measured for the joint structure of the subtalar joint, and the footprint areas of the ligament attachments of the cervical ligament, interosseous talocalcaneal ligament (ITCL), and anterior capsular ligament were measured for the ligament structure. Additionally, subtalar joint facets were classified into Degeneration (+) and (-) groups according to degeneration of the talus and calcaneus. No significant relationship was identified between the joint structure of the subtalar joint and degeneration of the subtalar articular facet. In contrast, footprint area of the ITCL was significantly higher in the Degeneration (+) group than in the Degeneration (-) group for the subtalar joint facet. These results suggest that the joint structure of the subtalar joint may not affect degeneration of the subtalar articular facet. Degeneration of the subtalar articular facet may be related to the size of the ITCL.
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Instabilidade Articular , Articulação Talocalcânea , Humanos , Articulação do Tornozelo , Ligamentos ArticularesRESUMO
Introduction: Adipose-derived stem cells (ASCs) secrete various growth factors to promote wound healing and to regenerate various tissues, such as bone, cartilage, and fat tissue. Subcutaneous adipose tissue is a considerable cell source in clinical practice and can be collected relatively easily and safely under local anesthesia. Moreover, platelet-rich plasma (PRP), a plasma component containing many platelets purified by centrifuging the collected blood, also promotes wound healing. PRP can be easily gelled and is therefore attracting attention as a scaffolding material for transplanted cells. The usefulness of a mixture of ASCs and PRP for periodontal tissue regeneration has been in vitro demonstrated in our previous study. The aim of this study is to present the protocol of translation of tissue regeneration with ASCs and PRP into practical use, evaluating its efficacy. Methods: This study is a multicenter, randomized, open-label comparative clinical trial. Fifteen patients will be randomly assigned to the treatment with mixture of ASCs and PRP or enamel matrix derivate administration into periodontal tissue defects. Increase in height of new alveolar bone in the transplanted area will be evaluated. The evaluation will be performed using dental radiographs after 36 weeks of transplantation. Occurrence of adverse events will be evaluated as secondary outcome. Results: This clinical study was initiated after meeting the regulations to be complied with, including ethical review and regulatory notifications. Conclusions: If effective, this cell therapy using autologous mesenchymal stem cells can represent a useful medical technology for regeneration of periodontal defects.
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PURPOSE: The aim of this study was to assess the response of dental pulp associated with donor or host cells in the pulp chamber and root canal after extra-oral transplantation. METHODS: Wild type or green fluorescent protein (GFP) transgenic first molars from 3-week, 6-week, and 12-week mice were transplanted into the subcutaneous layer of GFP mice or wild type mice. The teeth were histologically and immunohistochemically examined at 5 weeks after transplantation. RESULTS: Blood vessels present in the original coronal pulp had anastomosed with those from the recipient tissue that had invaded the root canal. Two distinct eosin-stained extracellular matrices were observed in the pulp chamber and root canal. Acellular matrix composed of nestin-positive, odontoblast-like cells invaded from the outside and was seen in the root canal of 3-week teeth. Cellular matrix comprising alkaline phosphatase (ALP)-positive fibroblast-like cells appeared in the original coronal pulp. In the root canal of the 6-week and 12-week teeth, cellular extracellular matrix consisting of ALP-positive fibroblast-like cells had invaded the recipient tissue. CONCLUSION: Dental pulp from immature teeth might be able to regenerate dentin-like tissue. This model could be useful in the development of an optimized vitalization treatment.
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Polpa Dentária , Odontoblastos , Animais , Cavidade Pulpar , Camundongos , Regeneração , Tela SubcutâneaRESUMO
This study aimed to examine the optimal cross-link density of recombinant peptide (RCP) particles, based on human collagen type I, for bone reconstruction in human alveolar cleft. Low- (group 1), medium- (group 2), and high- (group 3) cross-linked RCP particles were prepared by altering the duration of the heat-dependent dehydration reaction. Rat palatine fissures (n = 45), analogous to human congenital bone defects, were examined to evaluate the potential of bone formation by the three different RCP particles. Microcomputed tomography images were obtained to measure bone volume and bone mineral density at 4, 8, 12, and 16 weeks post grafting. Specimens were obtained for histological analysis at 16 weeks after grafting. Additionally, alkaline phosphatase and tartrate acid phosphatase staining were performed to visualize the presence of osteoblasts and osteoclasts. At 16 weeks, bone volume, bone mineral density, and new bone area measurements in group 2 were significantly higher than in any other group. In addition, the number of osteoblasts and osteoclasts on the new bone surface in group 2 was significantly higher than in any other group. Our results demonstrated that medium cross-linking was more suitable for bone formation-and could be useful in human alveolar cleft repairs as well.
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INTRODUCTION: This study aimed to examine the bone-forming ability of medium-cross-linked recombinant collagen peptide (mRCP) particles developedbased on human collagen type I, contains an arginyl-glycyl-aspartic acid-rich motif, fabricated as bone filling material, compared to that of the autologous bone graft. METHODS: Calvarial bone defects were created in immunodeficient rats though a surgical procedure. The rats were divided into 2 groups: mRCP graft and tibia bone graft (bone graft). The bone formation potential of mRCP was evaluated by micro-computed tomography and hematoxylin-eosin staining at 1, 2, 3, and 4 weeks after surgery, and the data were analyzed and compared to those of the bone graft. RESULTS: The axial volume-rendered images demonstrated considerable bony bridging with the mRCP graft, but there was no significant difference in the bone volume and bone mineral density between the mRCP graft and bone graft at 4 weeks. The peripheral new bone density was significantly higher than the central new bone density and the bottom side score was significantly higher than the top side score at early stage in the regenerated bone within the bone defects. CONCLUSION: These results indicate that mRCP has a high potential of recruiting osteogenic cells, comparable to that of autologous bone chips.
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An inferior alveolar nerve (IAN) injury is a common clinical problem that can affect a patients' quality of life. Cellular therapy has been proposed as a promising treatment for this injury. However, the current experimental models for IAN injury require surgery to create bone windows that expose the nerve, and these models do not accurately mimic human IAN injuries. Therefore, in this study, a novel experimental model for IAN injury has been established in rats. Using this model, the effects of Schwann cells and their role in the recovery from IAN injuries were investigated. Schwann cells were isolated from rat sciatic nerves and cultured. The first molar in the mandible was extracted and the IAN was immediately injured for 30 min by inserting an insect pin. Then, the Schwann cells or culture medium were transplanted into the extracted sockets of the cell and injury groups, respectively. After the surgery, the cell group displayed significantly increased sensory reflexes in response to mechanical stimulation, regenerated IAN width, and myelin basic protein-positive myelin sheaths when compared with the injury group. In conclusion, a novel animal experimental model for IAN injury has been developed that does not require the creation of a bone window to evaluate the impacts of cell transplantation and demonstrates that Schwann cell transplantation facilitates the regeneration of injured IANs.
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Traumatismos do Nervo Trigêmeo , Animais , Transplante de Células , Humanos , Nervo Mandibular , Qualidade de Vida , Ratos , Células de SchwannRESUMO
INTRODUCTION: In the present study, we examined the effect of oriented collagen tube (OCT) implantation on the recovery of sensory function of the resected rat sciatic nerve. MATERIALS AND METHODS: After a 10-mm long portion of the sciatic nerve of a rat was resected, an OCT was placed in the site of nerve defect. Recovery of the sensory function was evaluated using Von Frey test every 3 days after surgery. The regenerated tissue were histologically and ultrastructurally analyzed 2 and 4 weeks after the surgery. RESULTS: The sensory reflexes of the OCT group were restored to the level of that of the intact group after 15 days. Hematoxylin and eosin staining revealed the cross-linking between the proximal and distal stumps after 2 weeks. After 4 weeks, Luxol Fast Blue and immunohistochemical staining revealed the presence of myelin sheath from the proximal to distal region of the regenerated tissue and S100B staining confirmed the presence of Schwann cells. Interestingly, no myelin sheath was ultrastructurally observed around the regenerated axons at the central region after 2 weeks. CONCLUSIONS: These results suggest that OCTs facilitate the recovery of sensory function. Additionally, the non-myelinated axons contributed to the recovery of the sensory function.
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Periodontitis is one of the diabetic complications due to its high morbidity and severity in patients with diabetes. The prevention of periodontitis is especially important in diabetic patients because the relationship between diabetes and periodontitis is bidirectional. Here, we evaluated the impacts of glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on the amelioration of periodontitis. Five-wk-old Male Sprague-Dawley (SD) rats (n = 30) were divided into 3 groups: normal, periodontitis, and periodontitis with liraglutide treatment groups. Periodontitis was induced by ligature around the maxillary second molar in SD rats. Half of the rats were administered liraglutide for 2 weeks. Periodontitis was evaluated by histological staining, gene expressions of inflammatory cytokines in gingiva, and microcomputed tomography. Periodontitis increased inflammatory cell infiltration, macrophage accumulation, and gene expressions of tumor necrosis factor-α and inducible nitric oxide synthase in the gingiva, all of which were ameliorated by liraglutide. Liraglutide decreased M1 macrophages but did not affect M2 macrophages in periodontitis. Moreover, ligature-induced alveolar bone resorption was ameliorated by liraglutide. Liraglutide treatment also reduced osteoclasts on the alveolar bone surface. These results highlight the beyond glucose-lowering effects of liraglutide on the treatment of periodontitis.
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Processo Alveolar/efeitos dos fármacos , Complicações do Diabetes/metabolismo , Gengiva/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Liraglutida/farmacologia , Periodontite/metabolismo , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/metabolismo , Perda do Osso Alveolar/patologia , Processo Alveolar/diagnóstico por imagem , Processo Alveolar/metabolismo , Processo Alveolar/patologia , Animais , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Complicações do Diabetes/diagnóstico por imagem , Complicações do Diabetes/genética , Complicações do Diabetes/patologia , Expressão Gênica/efeitos dos fármacos , Gengiva/metabolismo , Gengiva/patologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Ligadura , Macrófagos/efeitos dos fármacos , Masculino , Maxila/diagnóstico por imagem , Maxila/efeitos dos fármacos , Maxila/patologia , Doenças Maxilares/diagnóstico por imagem , Doenças Maxilares/metabolismo , Doenças Maxilares/patologia , Osteoclastos/efeitos dos fármacos , Periodontite/diagnóstico por imagem , Periodontite/genética , Periodontite/patologia , Periodonto/efeitos dos fármacos , Periodonto/metabolismo , Periodonto/patologia , Ratos , Ratos Sprague-Dawley , Microtomografia por Raio-XRESUMO
AIMS/INTRODUCTION: The association between diabetes and periodontal disease is considered to be bidirectional. However, there is still controversy surrounding the relationship between periodontal disease and type 1 diabetes. We investigated whether insulin improves periodontitis without any local treatments for periodontitis under type 1 diabetes conditions using the ligature-induced experimental periodontitis model. MATERIALS AND METHODS: Type 1 diabetic rats were induced by streptozotocin injection. Experimental periodontitis was induced by ligature in normal and diabetic rats. Half of the diabetic rats were treated with insulin. Two weeks after the ligature, periodontitis was evaluated. RESULTS: Insulin treatment significantly improved inflammatory cell infiltration and inflammatory cytokine gene expression, leading to suppression of alveolar bone loss, in the periodontitis of diabetic rats. Insulin also suppressed the periodontitis-increased nitric oxide synthase-positive cells in periodontal tissue of the diabetic rats. Even without induction of periodontitis, diabetic rats showed decreased gingival blood flow and an increased number of nitric oxide synthase-positive cells in the gingiva and alveolar bone loss compared with normal rats, all of which were ameliorated by insulin treatment. We further confirmed that insulin directly suppressed lipopolysaccharide-induced inflammatory cytokine expressions in THP-1 cells. CONCLUSIONS: There were abnormalities of periodontal tissue even without the induction of periodontitis in streptozotocin-induced diabetic rats. Insulin treatment significantly ameliorated periodontitis without local periodontitis treatment in diabetic rats. These data suggest the therapeutic impacts of insulin on periodontitis in type 1 diabetes.
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Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 1/complicações , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Periodontite/tratamento farmacológico , Animais , Humanos , Masculino , Periodontite/etiologia , Periodontite/patologia , Ratos , Ratos Sprague-DawleyRESUMO
IMPACT STATEMENT: The rat palatine fissure is anatomically similar to human alveolar cleft. In this study, we examined potential bone repair by an autologous bone implant and beta-tricalcium phosphate (ß-TCP) using rat palatine fissure as a model. Autologous bone chips or ß-TCP granules were implanted into the rat palatine fissure. Our model demonstrated that higher bone volume and bone mineral density were achieved with autologous bone graft than with ß-TCP. We have provided the first demonstration of the suitability of the rat palatine fissure as the implant site to simulate the transplantation of bone graft materials into human alveolar cleft.
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Substitutos Ósseos/farmacologia , Transplante Ósseo , Fosfatos de Cálcio/farmacologia , Fissura Palatina/terapia , Animais , Autoenxertos , Fissura Palatina/metabolismo , Fissura Palatina/patologia , Modelos Animais de Doenças , Humanos , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Bone marrow-derived mesenchymal stem cells (BMMSCs) remain the most widely used source of osteogenic cells in bone tissue engineering research. A cell-based treatment for alveolar ridge augmentation has received attention as an alternative to bone grafting. In the present study, BMMSC transplantation into tooth extraction sockets of C57BL/6J mice was evaluated for alveolar ridge regeneration. The first right maxillary molars were extracted, and then BMMSCs (PDGFRα+ Sca-1+ CD45- TER119- cells) isolated from femoral and tibial bone marrow were immediately transplanted into the extraction sockets. A control group underwent the same procedure except for BMMSC transplantation. Bone formation in the sockets was evaluated using micro-computed tomography and histological and immunohistochemical analyses. At 3 weeks, bone formation in the sockets was more advanced in the experimental group than in the control group. Histological analysis at 6 weeks after transplantation showed that the sockets in the experimental group also contained a greater quantity of bone marrow. Interestingly, socket bone mineral density was lower in the experimental group than in the control group at 6 weeks. These findings suggest that BMMSC transplantation accelerates bone healing and augments bone marrow formation in tooth extraction sockets.