The Role of Inflammasome NLPR3 in the Development and Therapy of Periodontitis

Periodontitis is a chronic inflammatory disease that affects tooth-supporting tissues and even leads to tooth loss. NLRP3 inflammasomes play a critical role in periodontitis pathogenesis. Aberrant activation or overexpression of NLRP3 inflammasomes in cellular players, including osteoclasts, osteoblasts, periodontal ligament fibroblasts, and leukocytes often contributes to cellular dysfunction and environment abnormality, thus resulting in the disorganization of ligament and alveolar bone. In this review, we mainly focus on the negative regulation of NLRP3 inflammasome in periodontitis and highlight the importance of NLRP3 inflammasome as a candidate therapeutic target in periodontitis treatment. Then we elucidate the development status of NLRP3 inflammasome inhibitors and show their application potential for treating periodontitis. In summary, this review reveals the recent progress and perspectives of NLRP3 inflammasome and the therapeutic potential of NLRP3 inflammasome inhibitors in periodontitis.     

晚期糖基化终末产物受体及其配体在骨代谢疾病中作用的研究进展

晚期糖基化终末产物受体(RAGE)是具有多种配体的免疫球蛋白超家族成员,参与多种疾病的发病机制,包括神经退行性疾病阿尔茨海默病、糖尿病并发症以及多种与衰老、炎症相关的疾病,在调节先天免疫反应中起着关键作用.RAGE及其配体不仅是多种炎症反应的重要细胞因子,而且在骨髓间充质干细胞、成骨细胞及破骨细胞均表达RAGE.近年来...     

Inhibiting the growth of periopathogenic bacteria and accelerating bone repair processes by using robusta coffee bean extract

BackgroundPeriodontitis is an inflammatory disease of the teeth-supporting tissues caused by microorganisms. Robusta coffee bean extract has antibacterial properties due to its caffeine, flavonoids, trigonelline, and chlorogenic acid contents. The robusta coffee bean extract also regulates alveolar bone healing through bone remodelling.AimThe study aimed to investigate robusta coffee bean extract to inhibit bacterial growth and accelerate bone repair in vitro and in vivo.MethodsThis study used the paper disc diffusion method with the research group of robusta coffee bean extract with concentrations of 50%, 25%, 12.5%, 6.25%, and negative control, as much as 20 and dripped onto the disc paper then placed on the surface of the agar media that had been inoculated with bacteria. The diameter of the inhibition zone was measured. Twenty periodontitis rat models were given 0.05 ml of the robusta coffee bean extract on the molars and put in a periodontal pocket for seven days. Rats were decapitated, and alveolar bone tissues were stained with HE and IHC staining. The number of osteoclasts, osteoblasts and BMP-2 was counted using a microscope. Statistical test with Kruskal Wallis followed by Mann Whitney showed a p-value of <0.05.ResultsThe average diameter of the inhibitory zone of robusta coffee bean extract showed that the P. gingivalis group of bacteria was higher than that of A. actinomycetemscomitans and S. viridans (p < 0.05) with a concentration of 50%. The average number of osteoblast cells increased, and the average number of osteoclast cells decreased in the 50% concentration group compared to the other groups (p < 0.05). BMP-2 expression in the robusta coffee bean extract group was 50% higher than in the other groups.ConclusionRobusta coffee bean extract has a periopathogenic antibacterial and accelerates alveolar bone repair.     

雷公藤甲素对去势小鼠骨质疏松模型破骨细胞分化的影响

目的 探究雷公藤甲素（TP）对去势小鼠骨质疏松模型破骨细胞分化的影响，并探讨其可能的分子机制。方法 建立去势小鼠骨质疏松模型，分为假手术组（Sham组）、卵巢切除去势组（OVX组）、雷公藤甲素组（TP组）、利维爱组（Livial组），造模后第3天给予对应药物处理。治疗6周后，采用TRAP染色检测左侧股骨干骺端的破骨细胞数量。Micro-CT重建三维骨结构图像，检测左侧胫骨干骺端的骨密度（BMD）、骨小梁数目（Tb.N）、骨体积分数（BV/TV）、骨表面积组织体积比（BS/TV）、骨小梁分离度（Tb.Sp），ELISA检测外周血中IL-6、TNF-α、骨形成标志物骨钙素（OC）、骨吸收标志物抗酒石酸酸性磷酸酶（TRAcp5b）含量。Western Blot检测右侧股骨组织中p65、p-p65、IκBα、p-IκBα蛋白表达水平。结果 骨小梁周围破骨细胞数量比较：OVX组与Sham组相比明显增加；TP组与OVX组相比明显减少；TP组与Livial组比较，差异无统计学意义。骨参数分析：OVX组与Sham组相比，小鼠骨组织的BMD、Tb.N、BV/TV、BS/TV均显著下降，而Tb.Sp显著升高（P＜0.01）；与OVX组相比，TP组和Livial组骨组织的BMD、Tb.N、BV/TV、BS/TV均显著升高，而Tb.Sp显著下降（P＜0.01）；TP组与Livial组比较，差异无统计学意义（P＞0.05）。IL-6、TNF-α、OC、TRAcp5b含量比较：OVX组的IL-6、TNF-α含量显著高于Sham组（P＜0.01）；各组间OC水平比较，差异无统计学意义（P＞0.05）；OVX组的TRAcp5b水平显著高于Sham组（P＜0.01）。蛋白表达水平：与Sham组相比，OVX组的p65、IκBα表达水平不变，而p-p65和p-IκBα表达水平显著升高（P＜0.01）；TP处理后，p65、IκBα表达水平不变，而p-p65和p-IκBα表达水平却显著降低（P＜0.01）；TP组与Livial组比较，两者间p65、IκBα、p-p65和p-IκBα表达水平差异无统计学意义（P＞0.05）。结论 TP抑制破骨细胞分化，改善了去势小鼠的骨量丢失，其分子机制可能与抑制炎症因子IL-6、TNF-α的表达及NF-κB信号通路的磷酸化水平有关。     

正五聚蛋白3在骨质疏松和骨折愈合中的研究进展

正五聚蛋白3(pentraxin 3,PTX3)作为一种多功能糖蛋白,在调节炎症反应、促进组织损伤部位修复、诱导乳腺等骨外部位的异位钙化及维持骨内稳态等生理病理过程中发挥重要作用。其在骨密度中的影响可能受到多种因素的作用,在PTX3基因敲除小鼠及骨质疏松症(osteoporosis,OP)患者中,PTX3的缺失会导致骨密度的下降,而在韩国社区“Dong-gu研究”中则发现血浆PTX3水平与男性老年患者的股骨颈骨密度呈负相关。在骨相关细胞方面,对于成骨细胞(osteoblast,OB)来说,PTX3在维持OP状态下OB的表型与功能具有重要作用;对于破骨细胞(osteoclast,OC)来说,炎症状态下的PTX3可通过刺激核因子κB受体活化因子配体(receptor activator of nuclear factor-κB ligand,RANKL)生成及与TNF刺激基因6 (TNF-stimulated gene 6,TSG-6)结合提高破骨细胞活性以促进骨吸收;对于间充质干细胞(mesenchymal stem cells,MSCs)来说,PTX3可通过PI3K/Akt信号通路促进...