基于RANKL/OPG通路探讨GsMTx4对大鼠正畸牙齿移动过程中压力侧牙周组织改建的影响

口腔生物医学 ›› 2022, Vol. 13 ›› Issue (3): 169-174.

基于RANKL/OPG通路探讨GsMTx4对大鼠正畸牙齿移动过程中压力侧牙周组织改建的影响

王贺,李易,张曼,张严匀,张苗苗

哈尔滨医科大学附属第一医院

收稿日期:2022-05-16 修回日期:2022-08-29 出版日期:2022-09-25 发布日期:2022-09-29
通讯作者: 张苗苗 E-mail:zhangmiaohlj@163.com

Effect of GsMTx4 on periodontal tissue reconstruction at the pressure side during orthodontic tooth movement in rats through RANKL/OPG pathway

Received:2022-05-16 Revised:2022-08-29 Online:2022-09-25 Published:2022-09-29
Contact: zhang miaomiao E-mail:zhangmiaohlj@163.com

摘要/Abstract

摘要： 目的：从RANKL/OPG通路探讨Piezo1蛋白通道的抑制剂GsMTx4对大鼠正畸牙齿移动过程中压力侧牙周组织改建的影响。方法：75只健康SD雄性大鼠构建正畸模型，随机分为对照、加力、加力+GsMTx4组。测量第一磨牙近中移动距离，HE染色观察上颌第一磨牙近中根压力侧牙周组织病理变化，免疫组化染色观察核因子-κB受体活化因子配体（RANKL）、骨保护素（OPG）在压力侧牙周组织的表达量及定位，并观察RANKL/OPG比值的变化，抗酒石酸酸性磷酸酶染色观察压力侧牙周组织中破骨细胞数量变化。结果：随着加力时间的延长，牙齿移动距离逐渐增加，加力组牙齿移动距离高于加力+GsMTx4组（P＜0.05）；加力组与加力+GsMTx4组RANKL、RANKL/OPG比值以及破骨细胞数量均呈现先升高后降低的趋势，OPG呈现逐渐上升的趋势，且加力+GsMTx4组的值低于加力组（P＜0.05）。结论：GsMTx4能够降低大鼠正畸牙齿移动过程中压力侧牙周组织中RANKL、OPG蛋白的表达，并且能够抑制破骨细胞的分化，从而降低骨吸收活动，进而抑制牙齿移动。

关键词: GsMTx4, 正畸牙齿移动, RANKL, OPG, Piezo1, 破骨细胞

Abstract: Objective: To explore the effect of the inhibitor GsMTx4 of Piezo1 protein channel on periodontal tissue reconstruction at the pressure side during orthodontic tooth movement in rats through RANKL/OPG pathway. Methods: The orthodontic model was established in 75 healthy male SD rats. The rats were randomly divided into control group, force group and force+GsMTx4 group. The mesial movement distance of the first molars was measured. HE staining was used to observe the pathological changes of periodontal tissue in the pressure side of the proximal root of the mandibular first molars. Immunohistochemical staining was used to observe the expression and localization of nuclear factor-κB receptor activator ligand (RANKL) and OPG in the periodontal tissue at pressure side. The change of the ratio of RANKL to osteoprotegerin (OPG) and the number of osteoclasts in periodontal tissues at the pressure side through tartrate-resistant acid phosphatase staining were observed. Results:With the extension of force time, the tooth movement distance gradually increased, and tooth movement distance in force group was higher than that in force+GsMTx4 group (P<0.05). RANKL, the ratio of RANKL/OPG and the number of osteoclasts in force group and force+GsMTx4 group showed a trend of increasing first and then decreasing, and OPG showed a gradual increasing trend. Compared with force group, the values in force+GsMTx4 group were all decreased (P<0.05). Conclusions: GsMTx4 can reduce the expression of RANKL and OPG proteins in the periodontal tissue at the pressure side during orthodontic tooth movement in rats, and inhibit osteoclasts differentiation, thereby reducing bone resorption activity and inhibiting tooth movement.

Key words: GsMTx4, orthodontic tooth movement, RANKL, OPG, Piezo1, osteoblast

王贺李易张曼张严匀张苗苗. 基于RANKL/OPG通路探讨GsMTx4对大鼠正畸牙齿移动过程中压力侧牙周组织改建的影响[J]. 口腔生物医学, 2022, 13(3): 169-174.

参考文献

[1]Krishnan V, Davidovitch Z. On a path to unfolding the biological mechanisms of orthodontic tooth movement [J]. J Dent Res, 2009, 88(7):597-608.
[2]Yamaguchi M. RANK/RANKL/OPG during orthodontic tooth movement [J]. Orthod Craniofac Res, 2009, 12(2):113-119.
[3]Katagiri T, Takahashi N. Regulatory mechanisms of osteoblast and osteoclast differentiation [J]. Oral Dis, 2002, 8(3):147-159.
[4]Schett G, Stolina M, Dwyer D, et al. Tumor necrosis factor alpha and RANKL blockade cannot halt bony spur formation in experimental inflammatory arthritis [J]. Arthritis Rheum, 2009, 60(9):2644-2654.
[5]Dutra EH, Nanda R, Yadav S. Bone Response of Loaded Periodontal Ligament [J]. Curr Osteoporos Rep, 2016, 14(6):280-283.
[6]Gudipaty SA, Lindblom J, Loftus PD, et al. Mechanical stretch triggers rapid epithelial cell division through Piezo1 [J]. Nature, 2017, 543(7643):118-121.
[7]Poole K, Herget R, Lapatsina L, et al. Tuning Piezo ion channels to detect molecular-scale movements relevant for fine touch [J]. Nat Commun, 2014, 5(3520).
[8]Lee W, Guilak F, Liedtke W. Role of Piezo Channels in Joint Health and Injury [J]. Curr Top Membr, 2017, 79(263-273).
[9]Ikeda R, Arimura D, Saito M. Expression of Piezo mRNA is unaffected in a rat model of knee osteoarthritis [J]. Mol Pain, 2021, 17(17448069211014059).
[10]Eijkelkamp N, Linley JE, Torres JM, et al. A role for Piezo2 in EPAC1-dependent mechanical allodynia [J]. Nat Commun, 2013, 4(1682).
[11]Gottlieb PA , Sachs F. Piezo1: properties of a cation selective mechanical channel [J]. Channels (Austin), 2012, 6(4):214-219.
[12]Liu H, Bian W, Yang D, et al. Inhibiting the Piezo1 channel protects microglia from acute hyperglycaemia damage through the JNK1 and mTOR signalling pathways [J]. Life Sci, 2021, 264(118667).
[13]Jiang Y, Guan Y, Lan Y, et al. Mechanosensitive Piezo1 in Periodontal Ligament Cells Promotes Alveolar Bone Remodeling During Orthodontic Tooth Movement [J]. Front Physiol, 2021, 12(767136).
[14] 康婷，黄世友，李鹏，等.Piezos离子通道在大鼠牙周组织中表达的实验研究[J]. 牙体牙髓牙周病学杂志，2012，24(05)：269-273.
[15]Jin Y, Li J, Wang Y, et al. Functional role of mechanosensitive ion channel Piezo1 in human periodontal ligament cells [J]. Angle Orthod, 2015, 85(1):87-94.
[16]张瑞林，孙瑶.正畸牙槽骨改建中RANKL/OPG动态变化特征及牙周组织细胞凋亡观察[J].口腔医学，2019，39(06)： 488-493.
[17]Pivonka P, Zimak J, Smith DW, et al., Theoretical investigation of the role of the RANK-RANKL-OPG system in bone remodeling [J]. J Theor Biol, 2010, 262(2):306-316.