壳寡糖对骨质疏松伴牙周炎大鼠骨代谢及IKK/NF-κB通路的影响

目的：探讨壳寡糖对骨质疏松伴牙周炎模型小鼠骨代谢和IKK/NF-κB通路的影响。方法：将30只大鼠随机分为3组,每组10只,分为对照组、去势牙周炎组和壳寡糖治疗组。除对照组外,其余2组大鼠均切除卵巢并涂抹牙龈卟啉单胞菌液,建立骨质疏松伴牙周炎模型。结扎手术后4周,以200 mg/kg灌胃壳寡糖治疗组大鼠,另2组灌胃等体积生理盐水,每天1次,连续90天。观察各组牙周组织变化,给药前、给药结束后检测大鼠骨密度。给药结束后,尾静脉采血,采用酶联免疫吸附法测定各组血清碱性磷酸酶（ALP）、骨钙素（BGP）和抗酒石酸酸性磷酸酶5b(TRACP5b)的含量。采用视诊和探诊相结合的方法得到各组大鼠的牙龈指数和牙周附着丧失;处死大鼠,取出上颌骨,测量釉-牙骨质界到牙槽嵴顶的距离,得到牙槽骨吸收值。采用H-E染色,对各组大鼠上颌骨牙体、牙周组织进行病理学观察。采用RT-PCR和蛋白免疫印迹法分别检测各组大鼠牙周组织中核因子κB (NF-κB)、IκB激酶（IKK）mRNA和蛋白表达水平。采用SPSS 22.0软件包对数据进行统计学分析。结果：对照组大鼠牙龈呈粉红色,探诊不出血;去势牙周炎组大鼠牙龈红肿,...     

壳寡糖对牙周炎大鼠牙槽骨吸收及Th17/Treg平衡和OPG/RANKL/RANK通路的影响

目的: 探讨壳寡糖对牙周炎大鼠牙槽骨吸收及Th17/Treg平衡和OPG/RANKL/RANK通路的影响。方法: 建立牙周炎大鼠模型,随机分为模型组、壳寡糖低剂量组、壳寡糖中剂量组、壳寡糖高剂量组和甲硝唑组,每组12只,另取12只作为对照组。分组处理后,评估牙龈指数、牙槽骨吸收值;H-E染色观察牙周组织病理形态学变化;流式细胞术检测外周血中Th17/Treg细胞比值;酶联免疫吸附试验（ELISA）检测各组大鼠血清中IL-17、TGF-β、RANKL、OPG水平,实时荧光定量PCR（qRT-PCR）检测各组大鼠牙周组织OPG、RANKL mRNA表达水平。采用SPSS 24.0软件包对数据进行统计学分析。结果: 与对照组相比,模型组大鼠牙周组织呈现牙周膜纤维束断裂、排列紊乱,毛细血管扩张、增生,炎症细胞浸润等病理损伤;牙龈指数、牙槽骨吸收值、Th17/Treg比值、血清RANKL及IL-17水平、牙周组织RANKL mRNA水平显著升高（P<0.05）,血清OPG及TGF-β水平、牙周组织OPG mRNA水平显著降低（P<0.05）。与模型组相比,壳寡糖低、中、高剂量组和甲硝唑组大鼠牙周组织病理损伤减轻;牙龈指数、牙槽骨吸收值、Th17/Treg比值、血清RANKL及IL-17水平、牙周组织RANKL mRNA水平显著降低（P<0.05）,血清OPG及TGF-β水平、牙周组织OPG mRNA水平显著升高（P<0.05）,且壳寡糖各组呈剂量依赖性,壳寡糖高剂量组与甲硝唑组相比,差异无统计学意义（P>0.05）。结论: 壳寡糖可促使Th17/Treg平衡恢复正常,上调OPG表达,下调RANKL表达,抑制牙周炎大鼠牙槽骨吸收,改善其临床症状。     

器官培养中骨吸收因子的相互作用

为了研究不同浓度脂多糖（ｌｉｐｏｐｏｌｙｓａｃｃｈａｒｉｄｅ，ＬＰＳ）、脂磷壁酸（ｌｉｐｏｔｅｉｃｈｏｉｃａｃｉｄ，ＬＴＡ）、肿瘤坏死因子（ｔｕｍｏｕｒｎｅｃｒｏｓｉｓｆａｃｔｏｒ，ＴＮＦ）及前列腺素Ｅ（ｐｒｏｓｔａｇｌａｎｄｉｎＥ，ＰＧＥ）的骨吸收作用和相互作用，采用４５Ｃａ标记的１９天胚胎鼠长骨干器官培养，用样品道比法定量分析。结果表明，上述因子均能在器官培养水平刺激骨吸收，与对照组相比差异有显著性（Ｐ＜０．０５）。低浓度的ＬＰＳ与ＴＮＦ、ＬＰＳ与ＰＧＥ、ＴＮＦ与ＰＧＥ相互作用，超过各因子单独作用之和（期望值）；ＬＰＳ与ＬＴＡ、ＴＮＦ与ＬＴＡ相互作用，等于期望值；而ＬＴＡ与ＰＧＥ相互作用，小于期望值。研究结果提示，多种骨吸收因子的相互作用在牙周病骨吸收发病机理中有重要意义。     

睾酮水平对牙周炎小鼠模型炎症性骨吸收的影响及机制探讨

目的：探讨睾酮水平对牙周炎小鼠模型炎症性骨吸收的影响及机制。方法：48只SD小鼠随机分为未结扎组、假手术组、去势组、去势+睾酮组4组,每组各12只,分别进行空白处理、去势模型和牙周炎模型构建。于结扎术后6周采集小鼠内眦静脉血,测定血清睾酮水平。处死小鼠后,取左侧上颌骨组织,进行苏木精-伊红染色和亚甲蓝染色,比较各组小鼠牙槽骨丧失量（alveolar bone loss,ABL）和牙槽骨吸收面积。利用实时荧光定量PCR测定牙龈组织中炎性细胞因子mRNA的表达,同时对血清睾酮水平与ABL、牙槽骨吸收面积及细胞因子进行相关性分析。采用SPSS 20.0软件包对数据进行统计学分析。结果：假手术组、去势组和去势+睾酮组小鼠血清睾酮水平显著低于未结扎组（P<0.05）;去势+睾酮组小鼠血清睾酮水平显著高于假手术组和去势组（P<0.05）;去势组小鼠血清睾酮水平显著低于假手术组（P<0.05）;去势+睾酮组小鼠ABL显著大于未结扎组、假手术组和去势组（P<0.05）,去势组小鼠ABL显著小于假手术组（P<0.05）;去势+睾酮组小鼠牙槽骨吸收面积显著大于未结扎组、假手术组和去势组（P<0.05）,去势组小鼠牙槽骨吸收面积显著小于假手术组（P<0.05）;假手术组、去势组和去势+睾酮组小鼠牙龈组织中白介素1β（IL-1β）mRNA、白介素6（IL-6）mRNA及肿瘤坏死因子α（TNF-α）mRNA水平显著高于未结扎组,白介素10（IL-10）mRNA水平显著低于未结扎组（P<0.05）;假手术组和去势组小鼠牙龈组织中IL-1β mRNA水平显著低于去势+睾酮组,去势组显著低于假手术组（P<0.05）;血清睾酮水平与ABL、牙槽骨吸收面积、IL-1β呈正相关（P<0.05）。结论：牙周炎小鼠睾酮水平降低,睾酮长期耗竭状态可减少牙槽骨炎症性骨吸收,可能通过降低IL-1β水平而实现。合理降低睾酮水平,有可能成为减少牙周炎患者牙槽骨吸收的治疗新思路。     

牙龈卟啉单胞菌诱导的耐受对小鼠牙槽骨吸收的影响

目的:研究牙龈卟啉单胞菌(P.gingivalis)诱导的耐受对小鼠骨吸收相关因子白细胞介素-1β(IL-1β)、骨保护素(OPG)/NF-κB受体激活蛋白配体(RANKL)表达水平,以及牙槽骨吸收的影响。方法:采用1×10~9CFU P.gingivalis口内涂布给菌5 d,磷酸盐缓冲液(PBS)洗脱后,再次口内涂布P.gingivalis给菌2 d,构建Balb/c小鼠牙周组织耐受模型。10 d后收集新鲜牙龈组织,采用western bolt检测牙龈组织中IL-1β、OPG和RANKL表达水平的变化。6周后,收集上颌骨,采用亚甲基蓝染色法检测牙槽骨吸收水平的改变。结果:耐受组小鼠牙龈组织中IL-1β表达水平较非耐受组降低,OPG/RANKL比值较非耐受组升高。亚甲基蓝染色结果显示,耐受组小鼠釉牙骨质界至牙槽嵴顶(ABC-CEJ)的距离小于非耐受组(P<0.01),说明耐受组小鼠牙槽骨吸收较非耐受组降低。结论:P.gingivalis诱导小鼠牙周组织耐受后,小鼠牙龈组织中骨吸收相关因子IL-1β分泌降低,OPG/RANKL比值升高,抑制了牙槽骨吸收。     

钛离子诱导骨吸收的现象及机制

钛及钛合金材料因其良好的抗腐蚀性、生物相容性在种植体等方面得到广泛应用,但是钛及其他离子会从植入物中缓慢释放出来,可能导致周围骨吸收造成种植体植入失败.植入材料及其磨损颗粒所释放出来的金属离子影响成骨细胞、破骨细胞的功能,改变成骨与破骨之间的调控机制,导致成骨减弱、破骨增强,引起骨质的吸收.     

应用Micro-CT研究矫治力对正畸牙齿移动及牙根吸收的影响

目的：了解不同矫治力作用下大鼠牙齿移动距离及牙根吸收情况,探索应用Micro?CT研究正畸牙齿移动过程中矫治力对牙根吸收的影响。方法10周龄健康雄性SD大鼠64只（220~270 g）,分别施以10 g （10 g力组）、30 g力（130 g力组）拉右侧上颌第一磨牙向近中移动建立实验动物模型,以对侧同名牙为对照牙。于加力后第3、7、14、28天处死动物,使用Micro?CT扫描上颌第一磨牙及周围牙槽骨,测量上颌第一磨牙近中移动距离,计算加力28 d上颌第一磨牙近中根的表面凹陷体积,进行统计学分析。结果加力后发生牙齿移动,10 g力组在加力14 d内,牙齿移动量小于30 g力组（P =0.039）,在加力28 d时大于30 g力组（P<0.05）。加力28 d,10 g力组、30 g力组的牙根表面凹陷总体积高于对照组（P=0.004）,30 g力组产生的牙根表面凹陷总体积高于10 g力组（P<0.001）。结论 Micro?CT可以对牙齿移动及牙根吸收进行可靠评价及量化分析。加力后28 d,10 g力组移动量较30 g力组大,相应产生牙根吸收较30 g力组少。     

多西环素对大鼠正畸移动牙根吸收影响的研究

目的：建立正畸牙根吸收动物模型,研究多西环素（DOXY）对根吸收组织的影响。方法：选用SD大鼠36只建立正畸牙移动根吸收动物模型,随机分为空白对照组（A组）、注射DOXY对照组（B组）、正常牙加力组（C组）、注射DOXY加力组（D组）。在加力的0、7、10、14 d分别处死各组大鼠。并取相应时段的标本制作组织切片,进行HE染色和TRAP染色,检测多西环素对根吸收组织的影响。用计算机图像分析技术定量比较上述实验结果。结果：①在所有实验周期内（除第14 d）,D组根吸收明显少于C组（P＜0．05）。 D组根吸收的平均值缓慢增加,而C组14 d时显示减少。②C组、D组牙根面的TRAP阳性细胞数均在第10 d到达峰值,第14 d开始下降。然而D组在受力10 d后根面的TRAP阳性细胞数明显少于C组（P＜0．05）。结论：多西环素可能对正畸牙根吸收及破骨细胞的募集有抑制作用。     

种植体间距对种植体周骨吸收影响的Meta分析

目的 通过系统评价及Meta分析的方法评估种植体间距（interimplant distance,IID）对种植体周骨吸收的影响。方法 电子检索截至2022年3月PubMed、Embase、Cochrane Library、WebofScience、CNKI、万方数据库有关不同IID对种植体周骨吸收影响的人群或动物研究,且对关键文献进行引文索引。结果 共9篇研究符合纳入标准,其中动物研究7篇,临床试验2篇。以3 mm作为标准IID,Meta分析结果：动物研究中IID=2 mm和IID=3 mm的边缘骨吸收量没有统计学差异[MD=0.05,95%CI(-0.10,0.19),P=0.54];临床试验表明IID=2 mm时的边缘骨吸收量稍大于3 mm,但没有统计学意义[MD=0.11,95%CI(-0.09,0.31),P=0.27]。IID=2mm或3mm时的垂直骨吸收量没有统计学差异[MD=-0.10,95%CI(-0.27,0.07),P=0.24]。结论 基于有限的证据,与IID=3 mm相比,IID=2 mm的表现与之相似。仍需要细化评估组别、改善评估方式,进一步证实IID与种植...     

可溶性CD14对LPS诱导人牙龈成纤维细胞活化的影响

目的:观察重组表达的sCD14对LPS的炎症介导作用的影响。方法:将异硫氰酸荧光素(fluoresceinisothiocyanate,FITC)标记的LPS分别和sCD14以及阳性对照内毒素中和蛋白(endotoxin neutralizing protein,ENP)孵育后,加入人牙龈成纤维细胞培养系统中,通过流式细胞仪测定LPS与细胞结合后的荧光强度;采用ELISA检测细胞培养上清中的TNF-α和IL-6的含量。结果:sCD14和ENP可导致细胞膜平均通道荧光强度减低,LPS诱导的细胞因子TNF-α和IL-6分泌量显著下降。结论:sCD14和ENP使人牙龈成纤维细胞的LPS结合量显著下降,表明sCD14和LPS中和蛋白可竞争性结合LPS,引起细胞培养系统中游离LPS浓度下降,对细胞的炎症介导作用减小。     

正畸牙根吸收过程中牙根三维形态的MICRO-CT初步研究

目的了解不同的矫治力作用下牙根表面的三维形态学特征变化,探索正畸牙根吸收过程中矫治力值对牙根吸收的影响规律。方法选择11周龄的SD雄性大鼠22只,分别施加100g和30g近中移动上颌第一磨牙建立实验动物模型,以对侧同名牙作为对照牙。2周后处死动物,获得上颌第一磨牙及其周围牙槽骨。使用Skyscan 1172型Micro-CT扫描大鼠上颌第一磨牙,计算大鼠上颌第一磨牙近中根的表面凹陷体积并进行统计学分析。结果施加矫治力2周后,重力组与轻力组在牙根表面凹陷总体积上没有显著性差异,但是二者都显著高于对照组。在牙根上段近中面的凹陷体积上,轻力组显著高于重力组和对照组。在牙根下段远中面,重力组显著高于对照组（P〈0.01）。结论施加矫治力后,发生牙根吸收,但是在本实验的研究周期中,力值对牙根吸收的程度无明显影响,对吸收的部位有影响。在重力作用下,牙根吸收主要发生在牙根下段远中面。而在轻力作用下,牙根吸收主要发生在牙根上段近中面。     

Inhibition of 5‐lipoxygenase attenuates inflammation and bone resorption in lipopolysaccharide‐induced periodontal disease

1 Background

Arachidonate‐5‐lipoxygenase (5‐LO) activity and increased leukotriene B4 (LTB4) production have been implicated in various inflammatory conditions. Increased production of leukotrienes has been associated with periodontal diseases; however, their relative contribution to tissue destruction is unknown. In this study, an orally active specific 5‐LO inhibitor is used to assess its role in inflammation and bone resorption in a murine model of lipopolysaccharide (LPS)‐induced periodontal disease.

2 Methods

Periodontal disease was induced in Balb/c mice by direct injections of LPS into the palatal gingival tissues adjacent to the maxillary first molars three times per week for 4 weeks. Animals were treated with biochemical inhibitor (2 mg/kg/daily) or the same volume of the vehicle by oral gavage. Microcomputed tomography analysis was used to assess bone resorption. Enzyme immunoassay determined LTB4, and enzyme‐linked immunosorbent assays quantified tumor necrosis factor (TNF), interleukin (IL)‐12, and IL‐10 in gingival tissues. Histologic sections were used for the morphometric analysis (number of neutrophils and mononuclear cells). Osteoclasts were counted in tartrate‐resistant acid phosphatase–stained sections.

3 Results

Administration of 5‐LO inhibitor effectively reduced production of LTB4 (23.7% decrease) and significantly reduced TNF and IL‐12 levels in gingival tissues. Moreover, reduction of LTB4 levels in gingival tissues was associated with a significant decrease in bone resorption and a marked reduction in number of osteoclasts and inflammatory cells.

4 Conclusion

5‐LO activity plays a relevant role in inflammation and bone resorption associated with the LPS model of experimental periodontal disease.     

TNF、IL—1、IL—6刺激培养新生儿小鼠颅盖骨骨吸收的实验研究

目的：研究肿瘤坏死因子、白细胞介素－1、白细胞介素－6对培养的新生小鼠颅盖骨骨吸收的刺激作用。方法：采用器官培养法培养新生儿小鼠的颅盖骨,在3种细胞因子作用48h后,用原子吸收光谱仪测定上清液内钙含量。结果：3种细菌因子在实验浓度范围内均能促进上清 中钙含量增加,并且具有一定的剂量依赖特点,结论：肿瘤坏死因子、白细胞介素－1、白细胞介素－6能够刺激新生小鼠颅盖骨的骨吸收,是与骨吸收密切相关的细胞因子。     

壳聚糖体外抑菌实验研究

目的 研究3种壳聚糖（壳聚糖-Zn配合物、壳聚糖-Ag配合物、N，O-羧甲基壳聚糖）对4种感染根管致病菌的抑制作用。方法国际参考菌株选用牙髓卟啉单胞菌、牙龈卟啉单胞菌、中间普氏菌和粘性放线菌，以洗必泰作为对照，采用杯碟法进行抑菌实验，通过观察最小抑菌浓度（MIC）和测量抑菌环直径大小测定实验药物对受试细菌的抑菌作用。结果 3种壳聚糖的抑菌效果较强。与对照组洗必泰对各个受试菌的MIC值无统计学差异；1％壳聚糖-Zn配合物、1％壳聚糖-Ag配合物、1％N，O-羧甲基壳聚糖与2％洗必泰的抑菌效果无显著差异。结论 3种壳聚糖对根管感染的主要相关菌有显著抑制作用。     

Effect of fluoride on root resorption following heavy and light orthodontic force application for 4 weeks and 12 weeks of retention

Objective:To evaluate the null hypothesis that fluoride intake via drinking water has no effect on orthodontic root resorption in humans after orthodontic force application for 4 weeks and 12 weeks of retention.Materials and Methods:Forty-eight patients who required maxillary premolar extractions as part of their orthodontic treatment were selected from two cities in Turkey. These cities had a high and low fluoride concentration in public water of ≥2 pm and ≤0.05 pm, respectively. The patients were randomly separated into four groups of 12 each: group 1HH, high fluoride (≥2 ppm) and heavy force (225 g); group 2LH, low fluoride (≤0.05 ppm) and heavy force; group 3HL, high fluoride and light force (25 g); and group 4LL, low fluoride and light force. Light or heavy buccal tipping force was applied on the upper first premolars for 28 days. At day 28, the left premolars were extracted (positive control side); the right premolars (experimental side) were extracted after 12 weeks of retention. The samples were analyzed with microcomputed tomography.Results:On the positive control side, under heavy force application, the high fluoride groups exhibited less root resorption (P  =  .015). On the experimental side, it was found that fluoride reduced the total volume of root resorption craters; however, this effect was not statistically significant (P  =  .237). Moreover, the results revealed that under heavy force application experimental teeth exhibited more root resorption than positive control groups.Conclusion:The null hypothesis could not be rejected. High fluoride intake from public water did not have a beneficial effect on the severity of root resorption after a 4-week orthodontic force application and 12 weeks of passive retention.     

Effects of T cell adoptive transfer into nude mice on alveolar bone resorption induced by endotoxin

Using the method of reconstitution of nude mice with T cells, we examined the effects of T cell on alveolar bone resorption induced by repeated injections of Escherichia coli endotoxin into periodontal tissue. Three mice groups (normal, nude and T cell reconstituted nude mice) were used. Endotoxin derived from E. coli was repeatedly injected into the gingiva of the mice left mandibles every 48 h and the mice were killed on the day after the 1st, 4th, 7th, 10th, 13th and 20th injections of endotoxin. Alveolar bone resorption was examined histopathologically and histomorphometrically. Bone surfaces in contact with the osteoclast were defined as the site of active resorption and the ratios of active resorption were compared among the 3 nice groups. Consequently, no active resorption was found after the first injection of endotoxin in any group. After the 4th injection, active resorption was found in normal nice and T cell reconstituted nude mice and gradually rose with the increase in the injection frequency. In contrast, few osteoclasts were found even after the 10th injection in the nude mice. In addition, there were statistically significant differences between the normal price and nude mice after the 4th and 10th injections (p<0.05). These findings suggested that T cell influences periodontal bone destruction induced by local administration of endotoxin during the early phases.     

Inhibitory effect of 1,25-dihydroxyvitamin D3 on Porphyromonas gingivalis-induced inflammation and bone resorption in vivo

ObjectiveTo investigate whether intragastric administration of 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) could inhibit the bone resorption and inflammation in a mouse calvarial model infected by Porphyromonas gingivalis (P. gingivalis).DesignLive P. gingivalis ATCC 33277 was injected once daily for 6 days into the subcutaneous tissue overlying the calvaria in mice. At the same time, 1,25(OH)₂D₃ (50 μg/kg per day) was administered by gavage for 9 days, starting 3 d before the infection. Mice were killed under ether anesthesia 8 h after the last injection of P. gingivalis. Micro-computed tomography scanning was used to evaluate calvarial bone loss. Tartrate-resistant acid phosphatase was used to detect osteoclast activity. Real-time PCR was used to assess the mRNA expressions of OPG, RANKL, c-Fos, NFATc1, CTSK and TRAP in calvarial bone and IL-6, IL-10, IL-1β, IL-12p40 and TNF-α in soft tissue. The levels of serum IL-6, IL-10 were determined by ELISA.Results1,25(OH)₂D₃ treatment apparently attenuated bone resorption in P. gingivalis-induced mouse calvarial model and markedly reduced the number of osteoclasts. The expression levels of RANKL and osteoclast-related genes such as c-Fos, NFATc1, CTSK and TRAP were also decreased by 1,25(OH)₂D₃. Besides, 1,25(OH)₂D₃ inhibited the expression of pro-inflammatory cytokines IL-6, IL-12p40 and TNF-α and enormously elevated the expression of anti-inflammatory cytokine IL-10.Conclusion1,25(OH)₂D₃ may decrease bone resorption in vivo via suppressing the expression of osteoclast-related genes and its anti-inflammatory properties.