Receptor Activator of Nuclear Factor‐κB Ligand and Sclerostin Expression in Osteocytes of Alveolar Bone in Rats With Ligature‐Induced Periodontitis

Background: Osteocytes are increasingly recognized as significant sources of osteoclast differentiation factor, receptor activator of nuclear factor‐κB ligand (RANKL), and osteoblast differentiation inhibitory factor, sclerostin. In this study, RANKL and sclerostin expression of osteocytes is investigated in rats with ligature‐induced periodontitis. Methods: Rats were divided into control and periodontitis groups, and periodontitis was induced by ligature on the mandibular first molars. At 1, 3, 10, and 20 days after ligature, histologic analyses of alveolar bone (AB) and osteoid areas in the molar furcation were performed. The numbers of osteoclasts and RANKL‐ and sclerostin‐positive osteocytes were estimated by tartrate‐resistant acid phosphatase staining and immunohistochemistry, respectively. Results: The AB area gradually decreased at day 10 after ligature and increased at day 20. The number of osteoclasts markedly increased at day 3 and then decreased. Conversely, osteoid formation was suppressed up to day 3 and then showed a remarkable increase above control level at day 20. The number of RANKL‐positive osteocytes increased at days 1 and 3 and then decreased. Sclerostin‐positive osteocytes markedly increased at days 3 and 10 but decreased below control level at day 20. Conclusions: These results show that AB loss is accompanied by enhanced osteoclast formation and suppressed osteoid formation. Osteocytes express RANKL when osteoclast formation increases, and they express sclerostin when osteoid formation is suppressed. Conversely, osteocytic sclerostin expression decreases when osteoid formation increases. These findings suggest that osteocytes may be important in AB loss via RANKL and sclerostin expression in periodontitis.     

sclerostin在2型糖尿病伴牙周炎大鼠牙槽骨骨重建过程中的表达及意义

目的： 观察2型糖尿病（T2DM）伴牙周炎大鼠牙槽骨骨重建过程中骨硬化蛋白（sclerostin）的表达。方法： 将54只SD大鼠随机分为健康组、牙周炎组、T2DM伴牙周炎组,每组各18只。牙周炎组建立牙周炎大鼠模型,T2DM伴牙周炎组先建立T2DM模型,再建立牙周炎模型。腹腔注射STZ后1、5、10 d,检测糖代谢指标。结扎后8周,检测牙周指标。建模成功后1、3、6个月,免疫组织化学染色检测牙槽骨组织中sclerostin的表达。采用SPSS 21.0软件包对数据进行统计学分析。结果： 与未建模大鼠相比,T2DM建模大鼠腹腔注射STZ后1、5、10 d空腹血糖（FBG）,腹腔注射STZ后10 d空腹胰岛素（FINS）及胰岛素抵抗指数（HOMA-IR）均显著升高（P<0.05）。与未建模大鼠相比,牙周炎建模大鼠牙龈出血指数（SBI）、菌斑指数（PLI）、探针深度（PD）均显著增加（P<0.05）。与健康组相比,牙周炎组、T2DM伴牙周炎组建模成功后1、3、6个月牙槽骨组织中sclerostin表达显著增加（P<0.05）,且T2DM伴牙周炎组显著高于牙周炎组（P<0.05）。与建模成功后1个月相比,牙周炎组、T2DM伴牙周炎组建模成功后3、6个月牙槽骨组织中sclerostin表达显著增加（P<0.05）。与建模成功后3个月相比,牙周炎组、T2DM伴牙周炎组建模成功后6个月牙槽骨组织中sclerostin表达显著减少（P<0.05）。结论： sclerostin在牙周炎中表达增加,且合并T2DM进一步上调sclerostin的表达,但在骨重建过程中逐渐下调。     

实验性糖尿病牙周炎诱导骨细胞凋亡的初步研究

目的初步探讨糖尿病牙周炎条件下骨细胞的凋亡情况。方法选用6wk雄性SD大鼠62只,随机分为糖尿病牙周炎组（DP,n=22）、牙周炎（P,n=20）以及正常对照组（N,n=20）。采用一次性腹腔注射STZ（55mg/kg）的方法建立大鼠糖尿病模型,注射STZ后1wk检测血糖,血糖≥16.65mmol/L者定为糖尿病大鼠。采用丝线结扎大鼠上颌第二磨牙联合口内接种细菌的方法建立牙周炎模型。动物分别于丝线结扎后3wk和6wk分批处死,进行HE染色和原位细胞凋亡检测。观察指标包括：牙槽骨丧失（ABL）,骨细胞计数,骨细胞凋亡百分率。资料采用单因素方差分析统计学处理。结果丝线结扎后3周和6周,大鼠牙槽骨丧失在N组与P组、N组与DP组、P组与DP组不同,组间两两比较均有统计学意义（P〈0.05）,牙槽骨丧DP组〉P组〉N组。与N组比较,P组和DP组单位面积骨细胞数均减少,与P组比较,DP组单位面积骨细胞数亦显著减少（P〈0.05）。在丝线结扎后3周和6周,糖尿病牙周炎组（DP）骨细胞凋亡百分率均达到牙周炎组（P）的2倍左右。结论糖尿病条件下牙周炎骨丧失明显增加,糖尿病可加强牙周炎条件下牙周组织中骨细胞的凋亡,降低骨细胞的数量。     

Apoptosis of periodontium cells in streptozototocin- and ligature-induced experimental diabetic periodontitis in rats

Abstract

Objective. The aim of this study was to investigate the presence of apoptosis of periodontium cells in streptozototocin- and ligature-induced experimental diabetic periodontitis in rats. Materials and methods. Sixty-two 6-week-old male Sprague-Dawley (SD) rats were randomly divided into three groups: the diabetic periodontitis group (group DP; n = 22), periodontitis group (group P; n = 20) and normal control group (group N; n = 20). Diabetes was induced by intraperitoneal injection of streptozototocin (STZ). Periodontitis was initiated by ligating floss around maxillary second molars. The animals were sacrificed at 3 and 6 weeks after ligature placement in the P and DP groups. Maxillary dentoalveolar segments were isolated and were prepared for morphometric analysis of alveolar bone loss (ABL) and for histological analysis. Results. ABL was significantly increased in group DP compared with group P (p < 0.05). The number of PDL fibroblasts, osteoblasts and osteocytes in group DP was decreased compared with group P (p < 0.05). Inter-group analysis revealed higher osteoclast numbers in the inflammatory area of group DP and group P when compared with group N (p < 0.05). Also, compared with group P, group DP had more higher osteoclast numbers (p < 0.05). Periodontitis and diabetic periodontitis also increased apoptosis of fibroblasts, osteoblasts and osteocytes. The percentage of these apoptotic cells was ～ 2-fold higher in group DP vs group P. Conclusions. The results of these studies suggest that diabetes may have a negative effect on the periodontium by increasing the formation of osteoclasts and enhancing apoptosis of fibroblasts, osteoblasts and osteocytes in the periodontal tissue.     

Diabetes mellitus-associated periodontitis: differences between type 1 and type 2 diabetes mellitus

Aspriello SD, Zizzi A, Tirabassi G, Buldreghini E, Biscotti T, Faloia E, Stramazzotti D, Boscaro M, Piemontese M. Diabetes mellitus‐associated periodontitis: differences between type 1 and type 2 diabetes mellitus. J Periodont Res 2011; 46: 164–169. © 2010 John Wiley & Sons A/S Background and Objective: Although many studies have appeared about diabetes mellitus‐associated periodontitis, few have compared periodontitis inflammatory markers between type 1 (T1DM) and type 2 diabetes mellitus (T2DM), and information regarding this issue is scarce and contradictory. We evaluated the levels of plasma C‐reactive protein and of interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6) and tumour necrosis factor‐α (TNF‐α) in gingival crevicular fluid in two groups of subjects affected by T1DM and T2DM, in order to identify possible differences between the two classes in the inflammatory mechanisms of diabetes mellitus‐associated periodontitis. Material and Methods: Plasma C‐reactive protein and gingival crevicular fluidIL‐1β, IL‐6 and TNF‐α were measured in periodontitis patients affected by type 1 (P‐T1DM, n = 24) and type 2 diabetes mellitus (P‐T2DM, n = 24). Results: Gingival crevicular fluid levels of IL‐1β and TNF‐α in P‐T1DM subjects were significantly higher than in P‐T2DM subjects. In P‐T1DM subjects, we found significant negative correlations between the duration of diabetes mellitus and IL‐1β and between the duration of diabetes mellitus and TNF‐α. Conclusion: This study shows that IL‐1β and TNF‐α levels in periodontitis patients with T1DM are affected by the duration of diabetes mellitus.     

Hypertension favors the inflammatory process in rats with experimentally induced periodontitis

Bonato CF, do‐Amaral CCF, Belini L, Salzedas LMP, Oliveira SHP. Hypertension favors the inflammatory process in rats with experimentally induced periodontitis. J Periodont Res 2012; 47: 783–792. © 2012 John Wiley & Sons A/S Background and Objective: Cardiovascular diseases are significantly correlated with chronic periodontitis. The aim of this study was to evaluate bone‐loss level, neutrophil migration, CXCL2/CINC‐2α, CXCL5/LIX, CCL20/MIP‐3α and tumor necrosis factor‐α (TNF‐α) production, inducible nitric oxide synthase (iNOS) expression and C‐reactive protein (CRP) release in spontaneously hypertensive rats (SHRs) and normotensive (WTK) rats after experimental induction of periodontal disease. Material and Methods: Periodontitis was induced by placement of silk yarn ligatures around the first molar counterparts. The levels of CRP, CCL20/MIP‐3α and CXCL5/LIX were evaluated in the peripheral blood, and bone‐loss level, neutrophil recruitment, the production of myeloperoxidase, CXCL2, CXCL5, CCL20 and TNF‐α, and the expression of iNOS were evaluated in the gingival tissue. Histological sections were taken to evaluate and measure bone resorption and neutrophil recruitment in the furcation region. Results: Rats with periodontitis had alveolar bone resorption. SHRs with periodontitis showed marked bone loss and increased neutrophil infiltration in comparison with WTK rats. SHRs with periodontitis showed increased levels of TNF‐α and CXCL2, and a slight tendency for increased levels of CXCL5, in the gingival tissue but no increase in the level of CCL20. In SHRs, even without periodontitis, the levels of TNF‐α, CXCL2, CXCL5 and CCL20 showed a slight tendency to increase. In the WTK rats, TNF‐α, CXCL2 and CXCL5 levels were increased with periodontitis, but the level of CCL20 was not. iNOS was expressed in the gingival tissue of WTK rats and SHRs with periodontitis; however, SHRs appeared to express a higher level of iNOS than did WKT rats. The CRP level was elevated in both types of rats with periodontitis; however, the CRP level was higher in SHRs with periodontitis than in WTK rats with periodontitis. Conclusion: In SHRs, the hypertensive condition per se seems to favor the inflammatory processes that become potentiated with periodontitis, when compared with WKT rats.     

Involvement of toll‐like receptor 4 in alveolar bone loss and glucose homeostasis in experimental periodontitis

Watanabe K, Iizuka T, Adeleke A, Pham L, Shlimon AE, Yasin M, Horvath P, Unterman TG. Involvement of toll‐like receptor 4 in alveolar bone loss and glucose homeostasis in experimental periodontitis. J Periodont Res 2011; 46: 21–30. © 2010 John Wiley & Sons A/S Background and Objective: There is general agreement that certain fatty acids and lipopolysaccharides (LPS) promote inflammation through toll‐like receptor 4 (TLR4), and that inflammation promotes insulin resistance. We therefore hypothesized that mice with periodontitis and a TLR4 loss‐of‐function (LOF) mutation fed a high‐fat (HF) diet would develop improved glucose homeostasis compared with wild‐type (WT) animals with periodontitis fed a HF diet. Material and Methods: Wild‐type and TLR4 mutant mice fed a HF diet were divided into four groups (n = 6/group): WT; WT with periodontitis (WT/P); mutant (Mut); and mutant with periodontitis (Mut/P). Periodontitis was induced by placing LPS soaked ligatures around maxillary second molars. Fasting insulin and glucose levels were measured weekly for 10 wk. Glucose tolerance was evaluated at baseline (week 1) and at 9 wk. Insulin signaling (phosphorylation of Akt) and tumor necrosis factor‐α (TNF‐α) mRNA levels in liver were determined when the mice were killed at week 10. Results: Mut/P mice developed less alveolar bone loss compared with WT/P mice (p < 0.05). Fasting glucose levels were improved after 8 wk of feeding a HF diet (weeks 9 and 10) in Mut/P mice compared with Mut, WT and WT/P mice (p < 0.05). Glucose tolerance was impaired in all groups compared with baseline (p < 0.05), except for the Mut/P group. Insulin signaling was improved (p < 0.05), and expression of TNF‐α was decreased (p < 0.05) in the liver of Mut/P mice compared with the liver of WT/P mice. Conclusion: The TLR4 LOF mutation partially protects against alveolar bone loss and improves glucose homeostasis in mice with periodontitis fed a HF diet.     

非受体型蛋白酪氨酸磷酸酶2与核因子-κB在糖尿病牙周炎牙周组织破坏中的作用研究

目的观察糖尿病牙周炎条件下小鼠牙周组织中非受体型蛋白酪氨酸磷酸酶2（PTPN2）、核因子-κB（NF-κB）的表达与牙周组织破坏的关系。方法将4周龄健康雄性C57BL/6J小鼠随机分为正常对照组（N组）、单纯牙周炎组（P组）及糖尿病牙周炎组（DP组）,每组6只。采用口内接种牙龈卟啉单胞菌法在P组建立牙周炎模型,采用腹腔注射链脲佐菌素结合高脂高糖食物与口内接种牙龈卟啉单胞菌法在DP组建立糖尿病牙周炎模型。各组动物于P、DP组末次细菌接种4周后处死,通过体视显微镜观察牙槽骨形态和附着丧失面积,采用苏木精-伊红（HE）染色法观察牙周附着丧失的高度,免疫组织化学法检测牙周组织中PTPN2与NF-κB的表达强度。结果P、DP组牙槽骨的附着丧失面积和牙周附着丧失高度均高于N组（P<0.05）,PTPN2的表达量低于N组（P<0.05）,而NF-κB的表达量则高于N组（P<0.01）。结论在糖尿病牙周炎的发生发展过程中,NF-κB可能有促进作用,而PTPN2可能有抑制作用;PTPN2的表达减少可能导致NF-κB表达增强而加重牙周组织破坏。     

高压氧对牙周炎组织前列腺素的作用及机理分析

目的：探讨高压氧（hyperbaric oxygen,HBO)对鼠牙龈和牙槽骨中前列腺素E2（prostaglandins E2,PGE2）的作用，研究HBO治疗牙周炎的机理。方法：对60只豚鼠进行丝线缝扎和高糖食料喂养形成牙周炎，每天用0．25MPaHBO治疗牙周炎60min ，连续治疗2周，用酶联免疫测定法分析牙龈和牙槽骨中PGE2的含量，观察治疗组与对照组的PGE2变化。结果：对照组鼠牙 龈组织中的PGE2含量为3．21ng/g，牙槽骨中为3．22ng/g；牙周炎形成后牙龈组织和牙槽骨中的PGE2含量均明显升高（P＜0．01）；经HBO治疗后牙龈和牙槽骨中的PGE2含量较牙周炎组分别 降低了62．7％和69．6％，且与牙周炎组差异有极显著性。结论：牙 周炎形成后牙龈和牙槽骨中PGE2含量明显增高；HBO暴露后牙龈和牙槽骨中的PGE2含量均明显降低，且牙槽骨中PGE2的降低程度较牙龈组织更明显。     

Localization of SOST/sclerostin in cementocytes in vivo and in mineralizing periodontal ligament cells in vitro

Jäger A, Götz W, Lossdörfer S, Rath‐Deschner B. Localization of SOST/sclerostin in cementocytes in vivo and in mineralizing periodontal ligament cells in vitro. J Periodont Res 2009; doi: 10.1111/j.1600‐0765.2009.01227.x. © 2009 John Wiley & Sons A/S Background and Objective: Cementum and bone are rather similar hard tissues, and osteocytes and cementocytes, together with their canalicular network, share many morphological and cell biological characteristics. However, there is no clear evidence that cementocytes have a function in tissue homeostasis of cementum comparable to that of osteocytes in bone. Recent studies have established an important role for the secreted glycoprotein sclerostin, the product of the SOST gene, as an osteocyte‐derived signal to control bone remodelling. In this study, we investigated the expression of sclerostin in cementocytes in vivo as well as the expression of SOST and sclerostin in periodontal ligament cell cultures following induction of mineralization. Material and Method: Immunolocalization of sclerostin was performed in decalcified histological sections of mouse and human teeth and alveolar bone. Additionally, periodontal ligament cells from human donors were cultured in osteogenic conditions, namely in the presence of dexamethasone, ascorbic acid and β‐glycerophosphate, for up to 3 wk. The induction of calcified nodules was visualized by von Kossa stain. SOST mRNA was detected by real‐time PCR, and the presence of sclerostin was verified using immunohistochemistry and western blots. Results: Expression of sclerostin was demonstrated in osteocytes of mouse and human alveolar bone. Distinct immunolocalization in the cementocytes was shown. In periodontal ligament cultures, following mineralization treatment, increasing levels of SOST mRNA as well as of sclerostin protein could be verified. Conclusion: The identification of SOST/sclerostin in cementocytes and mineralizing periodontal ligament cells adds to our understanding of the biology of the periodontium, but the functional meaning of these findings can only be unravelled after additional in vitro and in vivo studies.     

Influence of antiplatelet drugs in the pathogenesis of experimental periodontitis and periodontal repair in rats

Background: Platelets contain an array of biologic mediators that can modulate inflammation and repair processes including proinflammatory mediators and growth factors. Previous studies have shown that periodontitis and periodontal repair are associated with platelet activation. We hypothesized that drug‐induced platelet inactivation may interfere in the processes of inflammation and repair in experimental periodontitis in rats by suppressing the release of biologic mediators from platelets to the site of injury. Methods: To measure the effects on periodontitis, ligatures were placed around first molars, and aspirin (Asp, 30 mg/kg) or clopidogrel (Clo, 75 mg/kg) was given intragastrically once daily for 15 days. Interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), and thromboxane A₂ levels were measured by enzyme‐linked immunosorbent assay. To evaluate the effects of antiplatelet drugs on periodontal repair, ligatures were removed after 15 days of periodontitis induction, and Asp or Clo were administered beginning the following day for 15 days. Periodontal repair was assessed by microcomputed tomography. Results: On periodontitis phase, Asp and Clo significantly reduced levels of TNF‐α and Il‐6 (P <0.05), but only Asp decreased thromboxane A₂ (P <0.05). Asp and Clo decreased inflammatory infiltration; however, this reduction was more pronounced with Clo treatment (P <0.05). Histometric analysis showed that Asp and Clo impaired alveolar bone resorption. During the repair phase and after removal of the ligatures, microcomputed tomography analysis demonstrated that treatment with Asp and Clo did not impair alveolar bone repair. Conclusion: Systemic administration of Asp and Clo attenuates the inflammation associated with periodontitis without affecting the repair process when stimulus is removed.     

"益肾清火"方对牙周炎大鼠牙槽骨重建的影响

目的:观察中药"益肾清火"方对牙周炎大鼠牙槽骨重建的影响。方法:选择12个月龄SD大鼠,分为A、B、C、D共4组,每组各6只动物。A组为空白对照组,B组为牙周炎造模组,C组为造模后灌服中药高剂量组,D组为造模后灌服中药等效剂量组。牙周炎造模成功后,A、B组动物灌喂生理盐水,C、D组动物灌喂中药3个月。方块截取各组动物牙槽骨,制作硬组织切片,行苦味酸-品红染色后,分析各组牙槽骨骨量、骨结构及骨转换参数的差异。采用SAS6.04软件包对数据进行单因素方差分析。结果:牙周炎大鼠灌服"益肾清火"方3个月后,与B组相比,C、D组类骨质形成明显增多,骨小梁密度较高、游离末端数少;A、B、C、D各组骨小梁面积百分数和结点末端比分别为:75.24±3.82/1.49±0.12、45.78±6.70/0.48±0.08、73.33±4.20/1.33±0.06和67.69±2.83/1.26±0.10。B组的2项参数均低于其余3组,统计学上有显著性差异(P<0.01)。各组类骨质面积(变量经转换)分别为(88.44±7.52)μm2、(145.37±13.91)μm2、(211.10±22.96)μm2和(201.22±24.75)μm2。A组类骨质面积比其余3组低,而B组又低于C、D2组,统计学上有显著性差异(P<0.01)。结论:中药"益肾清火"方有助于增加实验性牙周炎大鼠牙槽骨骨量,改善其骨质结构,促进骨的修复重建。     

骨硬化蛋白在骨组织改建中作用的分子机制

骨硬化蛋白是一种对成骨细胞具有抑制作用的蛋白，由骨细胞特异分泌后转运至成骨细胞，通过影响Wnt信号通路对成骨作用产生抑制。外部条件如激素水平、机械刺激以及低氧环境等都能影响骨硬化蛋白的表达。骨硬化蛋白抗体能够促进成骨细胞活性从而提高骨量，但其临床疗效和安全性还需进一步的研究确定。     

罗格列酮对牙周炎大鼠牙龈脂联素受体表达的影响

目的:探讨罗格列酮(ROS)对牙周炎大鼠牙龈脂联素受体1(AdipoRl) mRNA、脂联素受体2(AdipoR2) mRNA和TNF-α等炎症因子表达的影响及在牙周炎中对牙槽骨保护的潜能.方法:50只SD大鼠随机分为5组(n=10),大鼠不干预处理作为空白对照,40只大鼠用于制作牙周炎模型后分别用蒸馏水(牙周炎组)、1、3、10 mg/kg ROS(低、中、高剂量组)灌胃1次/d,持续4周.然后取样,RT-PCR测定牙龈组织AdipoR1和AdipoR2 mRNA表达水平,ELISA测牙龈组织TNF-α、MMP-9和血浆脂联素浓度,标准化的数码摄影测量釉牙骨质界到牙槽骨嵴顶(CEJ-A)距离.结果:牙周炎组和空白对照组相比,牙龈组织AdipoR1和AdipoR2的mRNA表达水平显著降低(P＜0.01),血浆脂联素水平无差异(P＞0.05),TNF-α和MMP-9浓度显著上升(P＜0.01).和牙周炎组相比,低、中、高剂量治疗组牙龈组织AdipoRl mRNA表达均升高(P＜0.05),TNF-α浓度显著降低(P＜0.01);中、高剂量治疗组牙龈组织AdipoR2 mRNA表达显著升高(P＜0.01),MMP-9浓度显著降低(P＜0.01),血浆脂联素浓度升高(P＜0.05),牙槽骨吸收量显著降低(P＜0.01).结论:ROS可能通过上调牙龈组织中AdipoR1和AdipoR2 mRNA表达水平,降低TNF-α、MMP-9浓度,缓解牙周组织炎症,降低牙槽骨吸收.     

The effect of spironolactone on experimental periodontitis in rats

BACKGROUND: Elevated levels of tumour necrosis factor (TNF) have been found in patients with adult periodontitis. Animal studies have shown that TNF plays an important role in the pathogenesis of periodontitis. New findings suggest that the aldosterone-inhibitor spironolactone possesses an anti-TNF effect. The purpose of the study was to determine the anti-TNF effect of spironolactone in an endotoxic shock rat model and to disclose the effect of oral administration of spironolactone on the development of experimental periodontitis in rats. METHODS: The study was divided in two parts. Part 1: oral administration of spironolactone (100 mg/kg) followed by intravenous lipopolysaccharide (1 mg/kg) infusion 45 min later. Blood samples were taken before and 90 min after lipopolysaccharide infusion to determine the TNF levels in spironolactone treated and non-treated rats. Part 2: oral administration of spironolactone [100 mg/(kg day)] starting 2 days prior to induction of experimental periodontitis established by peridental ligatures. Morphometrical and radiographical registrations of alveolar bone destruction were carried out to determine the effect of spironolactone on the progression of experimental periodontitis. RESULTS: In part 1 the endotoxic shock model showed a significant reduction in TNF levels in the spironolactone-treated group compared to the non-treated group, suggesting that spironolactone acts as a TNF inhibitor. In part 2 spironolactone-treated rats did not demonstrate significantly less alveolar bone destruction compared to non-treated rats. CONCLUSIONS: The insignificant effect of spironolactone treatment could be explained by the fast metabolism of spironolactone and that spironolactone does not completely inhibit TNF production in rats. Moreover, many other cytokines and mediators involved in alveolar bone destruction may account for the lacking response to spironolactone.     

Sclerostin and its role as a bone modifying agent in periodontal disease

BackgroundPeriodontitis is a highly prevalent inflammatory disease affecting the periodontium that results from an imbalance between periodontopathogens and host mechanisms. Continuous progression of the disease may lead to tissue and bone destruction, eventually resulting in tooth loss. The extent of bone loss depends on the dysregulated host immune response. Various host-elicited molecules play a major role in disease progression. The discovery of the glycoprotein sclerostin and its role as a regulator of bone mass has led to a better understanding of bone metabolism.HighlightSclerostin, which is primarily expressed by osteocytes, is a negative regulator of bone formation. It is a potent antagonist of the canonical Wingless-related integration site (Wnt) pathway, which is actively involved in bone homeostasis. Sclerostin is known to stimulate bone resorption by altering the osteoprotegerin (OPG)/receptor activator of nuclear factor kappa- β ligand (RANKL) balance. Additionally, in periodontitis, activation of the inflammatory cascade also increases the synthesis of sclerostin.ConclusionThe recently discovered sclerostin antibody has emerged as a positive therapeutic tool for the treatment of metabolic bone diseases. It has been reported to improve bone strength, bone formation, osseointegration around implants and lower the risk of bone fractures in various animal and human models. This review describes the properties and action of sclerostin, its role in periodontal diseases, and the advent and efficacy of sclerostin antibodies.     

Effects of Polycan,a β‐glucan,on experimental periodontitis and alveolar bone loss in Sprague‐Dawley rats

Kim YS, Kang SJ, Kim JW, Cho HR, Moon SB, Kim KY, Lee HS, Han CH, Ku SK, Lee YJ. Effects of Polycan, a β‐glucan, on experimental periodontitis and alveolar bone loss in Sprague‐Dawley rats. J Periodont Res 2012; 47: 800–810. © 2012 John Wiley & Sons A/S Background and Objective: Polycan is a promising candidate for the treatment of periodontal disease. This study was undertaken to examine whether Polycan, a type of β‐glucan, has a protective effect on ligature‐induced experimental periodontitis and related alveolar bone loss in Sprague‐Dawley rats. Material and Methods: Polycan was orally administered, daily, for 10 d, at 21.25, 42.5 or 85 mg/kg, beginning 1 d after ligation. Changes in body weight and alveolar bone loss were monitored, and the anti‐inflammatory effects of Polycan were determined by measuring the levels of myeloperoxidase (MPO), interleukin‐1beta (IL‐1β) and tumor necrosis factor‐alpha (TNF‐α) in gingival tissue. We also evaluated inducible nitric oxide synthase (iNOS) activity and malondialdehyde (MDA) concentrations as a measure of the antioxidant effect. Results: Ligature placement led to a marked decrease in body weight, increased alveolar bone loss and increased concentrations of MPO, IL‐1β, TNF‐α and MDA, as well as increased iNOS activity and inflammatory cell infiltration and decreased collagen‐fiber content. Histological examination revealed increases in the number and activity of osteoclast cells, decreases in alveolar bone volume and elevated percentages of osteclasts on the alveolar bone surface. Daily oral treatment with 42.5 or 85 mg/kg of Polycan for 10 d led to significant, dose‐dependent inhibition of the effect of ligature placement. Conclusion: Taken together, these results suggest that 10 d of oral treatment with Polycan effectively inhibits ligature placement‐induced periodontitis and related alveolar bone loss via an antioxidant effect.     

Orally Administered Liposomal Lactoferrin Inhibits Inflammation‐Related Bone Breakdown Without Interrupting Orthodontic Tooth Movement

Background: Bovine lactoferrin (bLF) modulates the production of tumor necrosis factor‐alpha (TNF‐α) and inhibits alveolar bone breakdown associated with periodontitis. This study is designed to examine the effects of orally administered liposomal bLF (LbLF) on orthodontic force (OF)‐induced alveolar bone remodeling during experimental tooth movement. Methods: Two groups of male Wistar rats were treated with either LbLF or control solution in drinking water 7 days before OF application. Lipopolysaccharide (LPS) was injected into the gingival sulcus in half the rats in each group. Thus, four groups: OF, OF+LbLF, OF+LPS, and OF+LPS+LbLF were established. Results: Orally administered LbLF significantly reduced apical migration of junctional epithelium in the OF and OF+LPS groups. In OF+LPS, osteoclast number in the alveolar crestal area was increased by LPS treatment, whereas osteoclast number was significantly reduced in OF+LPS+LbLF through suppression of TNF‐α production. Osteoclastic induction in the middle part, mainly from OF application, was not affected by LbLF administration. Inhibition of tooth movement was not induced by LbLF. Conclusions: Orally administered LbLF significantly inhibits LPS‐induced alveolar bone resorption but not OF‐induced bone remodeling. LbLF could be a potent therapeutic and preventive agent to control periodontal inflammation in patients undergoing orthodontic treatment.     

Group of serum inflammatory markers and periodontitis-metabolic syndrome coexistence in Koreans

Background: Recent epidemiologic studies have shown that individuals with periodontitis have a significantly increased risk of metabolic syndrome (MetS). Chronic infection and subsequent production of systemic inflammatory markers may be associated with this increased risk. The aim of present study is to determine whether the presence of periodontitis and MetS is associated with a group or an individual of C‐reactive protein (CRP), interleukin (IL)‐1β, IL‐6, IL‐8, tumor necrosis factor‐α (TNF‐α), and homocysteine (HCY) in the serum of a Korean population. Methods: Medical and periodontal parameters, including CRP, IL‐1β, IL‐6, IL‐8, TNF‐α, and HCY, were evaluated in 118 individuals (73 healthy; 20 with periodontitis only; 13 with MetS only; and 12 with both). The community periodontal index was used to assess periodontitis. Age, sex, monthly household income, smoking, and drinking were evaluated as confounders. Analysis of covariance, linear regression analysis, and factor analysis were applied. Results: The group of serologic cytokines was synergistically associated with the periodontitis–MetS coexistence. TNF‐α and IL‐6 were two representing serologic cytokines in the group. Conclusions: Our results suggest that a group of systemic biologic markers represented by TNF‐α and IL‐6 might mediate the association between MetS and periodontitis adjusted for various confounders. Additional evidence is needed to generalize our results more widely.     

Changes in the spatial distribution of sclerostin in the osteocytic lacuno-canalicular system in alveolar bone due to orthodontic forces,as detected on multimodal confocal fluorescence imaging analyses

Objective

Mechanical loading on the bone is sensed by osteocytes. Sclerostin is a molecule secreted by osteocytes that is downregulated by mechanical loading; therefore, its expression level is a potent sensor that indicates the spatial transduction of biomechanical properties in bone. This study applied macroconfocal microscopy to observe the spatial response of alveolar bone to orthodontic forces after immunofluorescence using anti-sclerostin antibodies.

Design

Orthodontic tooth movement with the Ni–Ti closed-coil spring was applied between the upper bilateral incisors and the left first molar of mice. Four days after this application, the animals were subjected to multimodal confocal fluorescence imaging analyses.

Results

Obvious downregulation of sclerotin in the osteocytic lacuna-canalicular system (LCS) was observed specifically in tensile sites of alveolar bone. Confocal-based three-dimensional fluorescence morphometry further quantitatively demonstrated that the distribution and expression of sclerostin in the tensile sites was significantly reduced compared to that observed in the corresponding control sites. Interestingly, the levels of sclerotin signals in the compression sites were significantly higher than those observed in the control sites, although the distribution of sclerotin was not significantly different.

Conclusions

Our observations suggest that spatial changes in the level and distribution of sclerostin in the alveolar LCS trigger successive bone remodelling due to orthodontic tooth movement. The multimodal confocal imaging analyses applied in this work will enhance comprehensive understanding regarding the spatial regulation of molecules of interest from the tissue to the cellular level.