Origin of mandibular condylar cartilage in mice,rats, and humans: Periosteum or separate blastema?

ObjectiveTo investigate if mandibular condylar cartilage is derived from the periosteum of the ossifying mandible or from a separate, programmed blastema.Materials and methodsFetal mice at E14.0–16.0, fetal rats at E16.0–18.0, and human embryos at 9 and 10 wks of gestation were used. The initial formation of rat condylar cartilage was investigated by using serial sections and enzyme-histochemistry to detect alkaline phosphatase activity. Histological observations of serial sections of human fetuses as well as 3D-reconstruction models were also analyzed. The expression of collagen type mRNA in developing rat condylar cartilage was directly compared with that in mice by performing in situ hybridization.ResultsAn anlage of the rat condylar process (condylar anlage) was clearly identified in the posterior position of the ossifying mandible and was continuous with it at E16.0. Newly formed rat condylar cartilage was observed at E16.5 and was continuous with the ossifying mandible. Mesenchymal cells in the condylar anlage at E16.0 showed alkaline phosphatase activity and chondrocytes in the newly formed condylar cartilage also showed enzymatic activity. Thus, rat mandibular condylar cartilage that derives from alkaline phosphatase-positive periosteum-like cells is continuous with the ossifying mandible, as previously demonstrated in mice, but rapid differentiation into hypertrophic chondrocytes in rats is not remarkable compared to that in mice. The condylar anlage and the newly formed cartilage were also continuous with the ossifying mandible in human embryos.ConclusionsMammalian mandibular condylar cartilage derives from the periosteum of the ossifying mandible in mice, rats, and humans.     

Changes in condylar cartilage after anterior mandibular displacement in juvenile pigs

Adaptive remodelling of the mandibular condyle in response to mandibular advancement is the mechanism exploited by orthodontic forward displacement devices.ObjectiveThis work investigated the expression of collagens, matrix metalloproteinases and vascular endothelial growth factor during this process.DesignTwenty juvenile pigs were randomly divided into two experimental groups, where the treatment group was fitted with mandibular advancement splints, and the control group was not. Changes in the mRNA content of condylar cartilage tissue was then were measured by real-time PCR using specific primers after 4 weeks of treatment.ResultsThe temporal pattern of the expression of Col1 and MMP13 during condylar adaptation coincided with that during natural condylar growth. The amount of the expression of Col10 during condylar adaptation was significantly lower (p < 0.05), whereas the expression of Col2, MMP8 and VEGF was significantly higher compared to natural growth (p < 0.05).ConclusionsIt is suggested that condylar adaptation in growing pigs triggered by mandibular forward positioning results not only from passive adaptation of cartilage, but also involves growth affected processes. Our results showed that mechanical strain produced by mandibular advancement induced remodelling and revascularization in the posteriocranial mandibular condyle. These results are mostly consistent with former published histological and histomorphometrical analyses.     

Study on the effects of gradient mechanical pressures on the proliferation,apoptosis, chondrogenesis and hypertrophy of mandibular condylar chondrocytes in vitro

ObjectiveTo investigate the effects of gradient mechanical pressure on chondrocyte proliferation, apoptosis, and the expression of markers of chondrogenesis and chondrocyte hypertrophy.MethodsMandibular condylar chondrocytes from 5 rabbits were cultured in vitro, and pressed with static pressures of 50 kPa, 100 kPa, 150 kPa and 200 kPa for 3 h, respectively. The chondrocytes cultured without pressure (0 kPa) were used as control. Cell proliferation, apoptosis, and the expression of aggrecan (AGG), collagen II (COL2), collagen X (COL10), alkaline phosphatase (ALP) were investigated. Ultrastructures of the pressurized chondrocytes under transmission electron microscopy (TEM) were observed.ResultsChondrocyte proliferation increased at 100 kPa and decreased at 200 kPa. Chondrocyte apoptosis increased with peak pressure at 200 kPa in a dose-dependent manner. Chondrocyte necrosis increased at 200 kPa. The expression of AGG increased at 200 kPa. The expression of COL2 decreased at 50 kPa and increased at 150 kPa. The expression of COL10 and ALP increased at 150 kPa. Ultrastructure of the pressurized chondrocytes under TEM showed: at 100 kPa, cells were enlarged with less cellular microvillus and a bigger nucleus; at 200 kPa, cells shrank with the sign of apoptosis, and apoptosis cells were found.ConclusionsThe mechanical loading of 150 kPa is the moderate pressure for chondrocyte: cell proliferation and apoptosis is balanced, necrosis is reduced, and chondrogenesis and chondrocyte hypertrophy are promoted. When the pressure is lower, chondrogenesis and chondrocyte hypertrophy are inhibited. At 200 kPa, degeneration of cartilage is implied.     

The PI3K/Akt signalling pathway may play an internal role related to abnormal condylar growth: a preliminary study

Developmental deformity of the mandible is one of the most common craniofacial malformations and is closely related to abnormal condylar growth. In this study, the role of PI3K/Akt signalling in the regulation of chondrocyte proliferation and hypertrophic differentiation in the condylar cartilage was studied. Immunohistochemical staining was used to investigate the expression of PI3K and p-Akt in the rat condyle cartilage. Rat condylar chondrocytes were cultured for the investigation of chondrocyte proliferation and hypertrophic differentiation when PI3K/Akt was inhibited. In addition, organ culture of the rat mandibular condyle was performed to evaluate the condyle cartilage growth while PI3K/Akt was inhibited. PI3K-positive cells and p-Akt-positive cells showing cytoplasmic staining were found to be present in the condylar cartilage. Reduced cell proliferation was observed in the culture of rat condylar chondrocytes when PI3K/Akt was inhibited; however, the hypertrophic differentiation level was increased. The proliferative zone thickness of condylar cartilage in the experimental group was less than that in the control group (P = 0.00185), but the hypertrophic zone was greater than that in the control group (P = 0.01048). PI3K/Akt signalling exerts opposite influences on chondrocyte proliferation and hypertrophic differentiation of the condylar cartilage, and these data suggest that PI3K/Akt is a potential intracellular regulation signal pathway in condylar cartilage development.     

Osteochondral angiogenesis in rat mandibular condyles with osteoarthritis-like changes

ObjectiveTo investigate angiogenesis at the osteochondral junction and changes in expression of pro- and anti-angiogenic factors in rat mandibular condyles with osteoarthritis-like changes.MethodsIn order to evoke osteoarthritis-like lesions in mandibular condyles, disordered occlusion was created experimentally in rats. Osteochondral vascularity was assessed histologically at 20 and 24 weeks. Protein and mRNA levels of pro-angiogenic factors including vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF) and matrix metalloproteases 9 (MMP9), and anti-angiogenic factor chondromodulin-I (CHM-I) were investigated by means of immunohistochemical staining and real-time PCR.ResultsOsteochondral angiogenesis was demonstrated as increased numbers of vascular channels terminating in the calcified cartilage and non-calcified cartilage in 20- and 24-week experimental groups compared with controls (all P < 0.05). In the experimental groups, VEGF, CTGF and MMP9 were highly expressed in the tissues adjacent to the osteochondral junction. However, CHM-I was more expressed in the superior but not deep hypertrophic chondrocytes. Compared to their age-matched controls, the protein levels of VEGF and CTGF were higher in 20-week experimental group, and the protein and mRNA levels of CTGF, MMP-9, and CHM-I increased in the 24-week experimental group (all P < 0.05).ConclusionIn the present rat model, osteochondral angiogenesis was observed in mandibular condyles with osteoarthritis-like changes, accompanied with local upregulation of VEGF, CTGF and MMP9. Although the increase in CHM-I may moderate pro-angiogenic factors effects in the superior cartilage, the deficiency of deep hypertrophic chondrocytes to express CHM-I may permit vascular invasion into condylar cartilage.     

咬合干扰对大鼠髁突软骨细胞内质网应激及凋亡的影响

目的:探讨咬合干扰致大鼠髁突软骨退变过程中内质网应激及凋亡相关分子的表达情况。方法:30只8周龄SD大鼠,采用大鼠上颌第一磨牙粘接不良修复体造成咬合干扰大鼠模型,4、8、12周后取颞下颌关节,甲苯胺蓝染色、苏木精-伊红染色观察组织形态学变化,透射电镜观察超微结构,免疫组织化学染色检测GRP78、Caspase-12的表达情况。结果:实验组髁突软骨基质降解、细胞密度降低,内质网膨胀、断裂;GRP78阳性细胞率较对照组显著增多(P<0.05),Caspase-12阳性细胞率在8、12周时明显增加(P<0.05)。结论:咬合干扰后大鼠髁突软骨细胞发生内质网应激及内质网凋亡,可能是髁突软骨退变的重要机制之一。     

异常咬合对小鼠髁突软骨细胞内质网应激性凋亡的影响研究

目的探讨异常咬合对小鼠髁突软骨细胞内质网应激性凋亡的影响。方法选取6周龄雌性C57BL/6J小鼠54只,随机分为4组,分别饲养1、3、7、11周,其中饲养1、3、7周的小鼠(各12只)再随机分为对照组和单侧前牙反(unilateral anterior crossbite,UAC)组,饲养11周的小鼠(18只)再随机分为对照组、UAC组和去冠组(UAC刺激7周后去除UAC刺激继续饲养至11周),每组小鼠均为6只。各组小鼠处死取材后对髁突软骨进行HE染色、糖相关蛋白78(glucose-regulated protein 78,GRP78)和含半胱氨酸的天冬氨酸蛋白水解酶12(cysteinyl aspartate specific proteinase 12,Caspase12)免疫组织化学染色以及TUNEL染色。结果(1)HE染色结果显示:各饲养期对照组小鼠髁突软骨细胞层次鲜明,软骨内细胞排列整齐;UAC组小鼠髁突软骨内软骨细胞数目减少,排列紊乱,随着时间延长这些变化逐渐加重。与同饲养期对照组相比,UAC组小鼠髁突软骨细胞密度、软骨厚度均显著减小(均P<0.05);去冠组小鼠髁突软骨细胞分层情况明显改善,软骨细胞密度、软骨厚度较UAC组有显著增加(均P<0.05),而与同饲养期对照组相比,差异无统计学意义(均P>0.05)。(2)免疫组织化学染色、TUNEL染色结果显示:各饲养期对照组小鼠髁突软骨中GRP78阳性细胞在软骨浅层和深层均有分布,Caspase12阳性细胞主要分布在软骨深层,但数量均很少;UAC组小鼠髁突软骨中出现大量GRP78和Caspase12阳性细胞。UAC组小鼠髁突软骨GRP78、Caspase12和TUNEL阳性细胞率均高于同饲养期对照组(均P<0.05);去冠组小鼠髁突软骨GRP78、Caspase12和TUNEL阳性细胞率均显著低于UAC组(均P<0.05),而与同饲养期对照组相比,差异无统计学意义(均P>0.05)。结论异常咬合促进髁突软骨细胞内质网应激性凋亡,从而加重髁突软骨的退行性变。     

The influence of the closing and opening muscle groups of jaw condyle biomechanics after mandible bilateral sagittal split ramus osteotomy

ObjectiveTo investigate the influence of the closing and opening muscle groups of the jaw on mandibular stability after mandibular bilateral sagittal split ramus osteotomy (BSSRO).Materials and methodsTo establish finite element models of four conditions (the normal mandible, preoperative mandibular prognathism, postoperative (BSSRO) mandibular prognathism, and mandibular prognathism following virtual BSSRO), we imported Digital Imaging and Communications in Medicine (DICOM) data into three-dimensional reconstruction software. Finite element analysis software and statistical software were used for analysis of the condylar stress distribution as a function of condylar position during the actions of jaw closing and jaw opening muscle groups.ResultsThe stress distribution of the normal mandibular bilateral condyle was statistically different from the normal mandibular condyle, indicating that bilateral structures are asymmetrical. There was a significant difference in stress distributions with condyle position between healthy control patients and patients prior to mandibular prognathism surgery (P < 0.05). There was no significant difference in stress distributions between the normal mandible and the mandible following virtual surgery or real mandibular prognathism surgery. Additionally, there was no significant difference at 6 months after mandibular prognathism surgery (P > 0.05).ConclusionsBilateral structures of the normal mandible were asymmetrical. After mandibular bilateral sagittal split ramus osteotomy, variation of the force arms of closing and opening muscle groups of the jaw was one of the major factors influencing mandibular stability. Virtual surgery is a promising strategy for preoperative planning to improve surgical success and reduce complications.     

Evaluation of effects of activator treatment on mandibular growth by analyzing components of condylar growth and mandibular rotation

PurposeThe objective of this study is to clarify the effects of activator treatment on mandibular growth in relation to condylar growth and total rotation of the mandible, and to investigate the relationships between the treatment responses and pretreatment facial morphology.Materials and methodsThirty Japanese girls with Class II division 1 malocclusion treated with activator were examined. Mean age at the start of treatment was 9.6 ± 1.6 years. Mean treatment duration was 19 ± 4 months. Lateral cephalograms obtained before and after treatment were used to analyze skeletal changes during treatment. Regional superimposition analysis was performed to evaluate activator effects by decomposing the mandibular growth into condylar growth and mandibular total rotation.ResultsThe changes in intermaxillary relationships were significantly correlated with vertical condylar growth and mandibular total rotation (P < 0.05 and P < 0.01). The changes in the forward displacement of the mandible were significantly correlated with sagittal condylar growth and mandibular total rotation (P < 0.05 and P < 0.01). Vertical condylar growth and mandibular total rotation were significantly correlated with pretreatment mandibular morphology (P < 0.05 and P < 0.01).ConclusionBoth the sagittal condylar growth and counterclockwise mandibular total rotation attributed to activator treatment contribute to forward displacement of the mandible. The activator effects are expected greater in patients with flat mandibular plane, small gonial angle, backwardly inclined mandibular ramus and long posterior facial height.     

周期性单轴压力对大鼠髁突软骨细胞结缔组织生长因子表达的影响

目的 探讨在髁突软骨细胞受到周期性单轴压力后,结缔组织生长因子(connective tissuegrowth factor, CTGF)表达的影响,为正畸治疗中髁突软骨受力后的改建提供生物学依据。方法 选取1周龄SD大鼠,提取并培养髁突软骨细胞,免疫组化鉴定。利用四点弯曲细胞力学加载仪对第3代细胞进行力值为2000u strain、0.5Hz的体外周期性单轴压力加载,分别在加力0min、30min、60min和120min后继续培养24h,应用蛋白印迹法检测在不同加力时间CTGF蛋白表达的变化。应用SPSS18.0软件对数据进行统计学分析。结果 CTGF的相对蛋白量在加力0min、30min、60min和120min后,分别为0、1.59、2.34和3.16,随着加载时间的增加,表达呈逐渐上升趋势。且组间差异具有统计学意义(P<0.05) 结论 周期性单轴压力可刺激大鼠髁突软骨细胞CTGF的表达。     

Influence of chewing time on salivary stress markers

PurposeWe investigated the influence of chewing time on salivary stress markers.MethodsParticipants performed arithmetic calculations for 30 min as stress loading, followed by chewing for 0, 5, 10, or 15 min. All experiments finished at 25 min after stress loading. With 0-min chewing, saliva was collected before stress loading (BS), immediately after stress loading (R0), and at 5, 10, 15, and 25 min after stress loading (R5, 10, 15 and 25). With 5, 10, or 15 min chewing, saliva was collected at BS and R0, immediately after chewing (Ch5, 10 and 15, respectively), and 25 min after stress loading (Ch5R25, Ch10R25 and Ch15R25, respectively). Salivary alpha-amylase activity and cortisol levels were measured to evaluate stress. Change in stress markers between R0 and Ch5, 10 and 15 or R25, Ch5R25, Ch10R25 and Ch15R25 were calculated.ResultsNo significant differences were observed in rate of change in alpha-amylase activity among the chewing conditions. Rate of decrease in cortisol levels was significantly greater at 15-min chewing than at 5-min chewing. Rate of decrease in cortisol levels was significantly greater at 10 and 15-min chewing than at 0-min chewing.ConclusionThe present results indicate that chewing time affects the reaction of the endocrine system to mental stress, and that continuous chewing for more than 10 min is effective in reducing stress.     

不同静压力对新生SD大鼠髁突软骨细胞增殖与凋亡的影响

目的：探讨不同静压力对髁突软骨细胞增殖与凋亡的影响。方法：对培养到第3代新生SD大鼠髁突软骨细胞加载0、12、24、36kPa静压力1h后立即收集样本，用流式细胞仪检测细胞凋亡与增殖指数的变化。结果：随着压力的增加（0、12、24、36kPa），除24kPa外，细胞增殖指数和凋亡指数在加力结束时（0h）均减少（P〈0．05），其中，细胞增殖指数在36kPa加力结束时减幅最大，细胞凋亡指数则在12kPa加力结束时减幅最大。结论：在0、12、24、36kPa力值范围内，软骨细胞增殖、凋亡与应力值存在一定的关系，但这并非是简单的线性关系。     

Roles of hypoxia inducible factor-1α in the temporomandibular joint

ObjectiveTemporomandibular joint osteoarthritis (TMJ-OA) is a degenerative disease characterized by permanent cartilage loss. Articular cartilage is maintained in a low-oxygen environment. The chondrocyte response to hypoxic conditions involves expression of hypoxia inducible factor 1α (HIF-1α), which induces chondrocytes to increase expression of vascular endothelial growth factor (VEGF). Here, we investigated the role of HIF-1α in mechanical load effects on condylar cartilage and subchondral bone in heterozygous HIF-1α-deficient mice (HIF-1α^+/−).DesignMechanical stress was applied to the TMJ of C57BL/6NCr wild-type (WT) and HIF-1α^+/− mice with a sliding plate for 10 days. Histological analysis was performed by HE staining, Safranin-O/Fast green staining, and immunostaining specific for articular cartilage homeostasis.ResultsHIF-1α^+/− mice had thinner cartilage and smaller areas of proteoglycan than WT controls, without and with mechanical stress. Mechanical stress resulted in prominent degenerative changes with increased expression of HIF-1α, VEGF, and the apoptosis factor cleaved Caspase-3 in condylar cartilage.ConclusionOur results indicate that HIF-1α may be important for articular cartilage homeostasis and protective against articular cartilage degradation in the TMJ under mechanical stress condition, therefore HIF-1α could be an important new therapeutic target in TMJ-OA.     

RhoE regulates actin cytoskeleton organization in human periodontal ligament cells under mechanical stress

ObjectivesRhoE and regulator of G-proteins signalling (RGS) 2 were identified as the up-regulated genes in human periodontal ligament (PDL) cells under compression. RhoE belongs to the Rho GTPase family, and RGS2, a novel family of GTPase-activating proteins, turns off the G-protein signalling. Rho family proteins have recently been known to regulate actin cytoskeleton dynamics in various cell types. In this study, we investigated the involvement of RhoE and RGS2 in the regulation of actin filament organization in the PDL cells under mechanical stress.MethodsHuman PDL cells were cultured and subjected to a static compressive force (3.0 g/cm²) for 48 h. To observe changes in the actin cytoskeleton and the expression of RhoE and RGS2 in response to mechanical stress, immunofluorescence analysis was performed. To examine the role of RhoE and RGS2 in actin filament organization, cells were transfected with antisense S-oligonucleotides (ODNs) to RhoE and RGS2.ResultsCompressive force caused a loss and disassembly of actin stress fibres leading to cell spreading. Immunocytochemical study revealed that RhoE and RGS2 expressions were induced by mechanical stress and localized in the perinuclear and in the cell membrane, respectively. The impaired formation of stress fibres caused by compressive forces was recovered by treatment with antisense S-ODN to RhoE to the control levels. However, addition of antisense S-ODN to RGS2 did not affect the stress fibre formation.ConclusionsThese results indicate that the loss and disassembly of stress fibres due to mechanical stress are mediating RhoE signalling, without the exertion of RGS2.     

周期性单轴压应力对大鼠髁突软骨细胞Stress70/GRP75的早期影响

目的:探讨体外周期性单轴压应力对大鼠髁突软骨细胞糖调控蛋白Stress70/GRP75的早期动态变化影响。方法:利用四点弯曲细胞力学加载仪,对第3代大鼠髁突软骨细胞进行体外周期性单轴压应力加载,力值为4000μstrain,时间分别为0、15、30、60、120、240min;采用Western免疫印迹技术和图像分析技术,研究大鼠髁突软骨细胞糖调控蛋白Stress70/GRP75的动态变化,对结果进行单因素方差分析。结果:4000μstrain周期性单轴压应力作用下,大鼠髁突软骨细胞糖调控蛋白Stress70/GRP75的表达发生变化,0min条带灰度值为114.2±5.08;30min时降至最低,为86.1±5.09(P<0.001);60min后有所回升,至104.0±4.41(P<0.01),但仍表达下调;120min后表达开始增强,灰度值为134.5±3.74(P<0.001)。结论:4000μstrain压应力刺激,对大鼠髁突软骨细胞糖调控蛋白Stress70/GRP75存在时间效应性,初期表达下调;随着应力加载时间延长,其表达反馈增强。     

The effect of rheumatoid arthritis and functional loading on the structure of the mandibular condyle in a transgenic mouse model: An FTIR study

ObjectiveThe objective of the present study was to investigate the effect of rheumatoid arthritis and functional loading through diet modification on the biochemical properties of the mandibular condyle in a transgenic mouse model and compare with healthy littermates.DesignTwenty three, 4-week old hybrid male mice were used. Eleven were of transgenic line hTNF 197 (Tg 197 – with rheumatoid arthritis – RA) and 12 healthy littermates, both from mixed background CBAxC57BL/6. Four groups of mice were formed. Group 1 [n = 5, RA-hard] included transgenic mice and received ordinary (hard) diet; group 2 [n = 6, RA-soft] included transgenic line and received soft diet; group 3 [n = 6, control-hard] were healthy littermates receiving ordinary (hard) diet and group 4 [n = 6, control-soft] were healthy littermates with soft diet. Experimental period was 28 days. Following sacrifice, the mandibular condyles were subjected to micro-attenuated reflection Fourier transform infrared spectroscopy (micro-ATR FTIR) to reveal collagen/proteoglycan conformation of the condylar cartilage, while resin-embedded and metallographically polished specimens were evaluated through reflection FTIR microscopy to identify mineralization status of the corresponding condylar bone.ResultsThe multivariable analysis revealed significantly lower a-helix to amide I percentage area ratio for the transgenic animals after adjusting for diet (β = −4.29, 95% CIs: −8.52, −0.06; p = 0.04). Mineral phase indices did not differ significantly between RA and control groups regardless the type of diet.ConclusionsInternal derangement of the anatomical structure with denaturation in the collagen structural components of the mandibular condyles of the RA animals was found, while no association with functional loading through diet modification was recorded.     

Analisi agli elementi finiti per la definizione della distribuzione degli stress meccanici negli impianti

ObjectivesTo study a spiral family implant by finite element analysis (FEA) inserted in mandible, connected with straight abutment and loaded with vertical and lateral forces.Materials and methodsThe biomechanical behaviour of 5 mm × 13 mm Ultimate dental implant (AoN Implants, Grisignano di Zocco, Vicenza, Italy), connecting screw, straight abutment subjected to static loads, in contact with mandibular bone was evaluated by FEA.ResultsStress and strain values of fixture are comparable to those obtained by analyzing different spiral implants.ConclusionsThese implants can be used in mandibular bone. However, clinical studies are needed to verify the reported results.     

Dipeptidyl peptidase-4 inhibitor enhances restoration of salivary glands impaired by obese-insulin resistance

ObjectiveChronic high-fat diet consumption causes not only obese- insulin resistance, but also leads to pathological changes in salivary glands, including increased mitochondrial dysfunction, apoptosis, oxidative stress, and inflammation. Dipeptidyl peptidase-4 inhibitor (vildagliptin) is an oral anti-diabetic drug, using for treatment of type 2 diabetes. Vildagliptin has been shown to exert beneficial effects on several organs in cases of obese-insulin resistant condition. However, the effect of vildagliptin on salivary glands impaired by obese-insulin resistance has not been investigated. The hypothesis in this study is that vildagliptin confers beneficial effects on the salivary gland impaired by obese-insulin resistance via decreasing mitochondrial dysfunction, apoptosis, oxidative stress, and inflammation.DesignTwenty-four male Wistar rats were divided into two groups. Each group was fed with either a normal (ND; n = 8) or a high fat diet (HFD; n = 16) for 16 weeks. At week 13, the HFD-fed rats were subdivided into 2 subgroups to receive either a vehicle or vildagliptin (3 mg/kg/day) for 28 days via gavage feeding. ND-fed rats were treated with the vehicle. At the end of treatment, metabolic parameters were examined, and rats were killed. Submandibular glands were removed to appraise inflammatory markers, apoptosis and mitochondrial function.ResultsVehicle-treated HFD-fed rats developed obese-insulin resistance with an increase in oxidative stress, inflammation, apoptosis, and mitochondrial dysfunction in the salivary glands. Vildagliptin therapy reduced oxidative stress, inflammation, apoptosis and mitochondrial dysfunction in salivary gland of HFD-fed rats.ConclusionVildagliptin prevented salivary gland injury occurring due to obese-insulin resistance.     

Fetal jaw movement affects Ihh signaling in mandibular condylar cartilage development: The possible role of Ihh as mechanotransduction mediator

ObjectiveJaw movement is an important mechanical factor for prenatal development of the condylar cartilage of mandible. Fetal jaw movement restriction has been shown to cause deformity of the mandibular condyle. We hypothesized that this treatment affects the expression of mechanosensitive molecules, namely Indian hedgehog (Ihh) and Parathyroid hormone related protein (PTHrP) in the condyle.Experimental methodsWe restrained jaw movement by suturing the jaw of E15.5 mouse embryos and allowed them to develop until E18.5 using exo utero system, and analyzed them by immunohistochemistry and in situ hybridization methods.ResultsMorphological, histomorphometric and immunohistochemical study showed that the mandibular condylar cartilage was reduced and deformed, the volume and total cell numbers in the condylar cartilage were also reduced, and number and/or distribution of 5-bromo-2′-deoxyuridine-positive cells, Ihh-positive cells in the mesenchymal and pre-hypertrophic zones were significantly and correspondingly decreased in the sutured group. Using in situ hybridization, reduced expression of Ihh, PTHrP and their related receptors were observed in condylar cartilage of the sutured embryos.ConclusionsOur results revealed that the altered mechanical stress induced by prenatal jaw movement restriction decreased proliferating cells, the amount of cartilage, and altered expression of the Ihh and PTHrP, suggesting that Ihh act as mechanotransduction mediators in the development of mandibular condylar cartilage.