坏死性凋亡在大鼠牙移动过程中对牙周组织改建的影响

›› 2021, Vol. 41 ›› Issue (12): 1068-1072.

坏死性凋亡在大鼠牙移动过程中对牙周组织改建的影响

季开心¹,陈思言²,张敏杰³,张苗苗⁴

1. 哈尔滨医科大学附属口腔医院；哈尔滨医科大学附属第一医院
2. 哈尔滨医科大学附属第一医院
3. 哈尔滨医科大学附属口腔医院
4. 哈尔滨医科大学附属第一医院口腔医院

收稿日期:2021-04-02 修回日期:2021-07-21 出版日期:2021-12-28 发布日期:2021-12-31
通讯作者: 张苗苗 E-mail:zhangmiaohlj@163.com
基金资助:
哈医大一院科研创新基金

Effect of necroptosis on periodontal tissue remodeling during tooth movement in rats

Received:2021-04-02 Revised:2021-07-21 Online:2021-12-28 Published:2021-12-31

摘要/Abstract

摘要： [摘要]　目的　观察在大鼠牙齿移动过程中坏死性凋亡对牙齿移动及牙周组织中核因子κB受体活化因子配体（receptor activator of nuclear factor-κB ligand，RANKL）、骨保护素（osteoprotegerin，OPG）表达的影响。方法　建立大鼠上颌牙齿移动正畸模型，根据坏死性凋亡抑制剂Necrostatin-1（Nec-1）的使用情况，将大鼠随机分为对照组（A组）、抑制剂组（B组）、加力组（C组）、加力+抑制剂组（D组）。游标卡尺测量上颌第一磨牙前移距离，HE染色观察压力侧玻璃样变情况，免疫组化检测第1、3、7、10、14天压力侧牙周组织中RANKL、OPG的表达变化。结果　A组和B组中大鼠牙齿无移动，压力侧未出现玻璃样变区域，同时RANKL与OPG表达较少。C组与D组牙齿出现移动，在第3、7、10、14天时两组移动距离具有统计学差异（P<0.05）；C组第7天时RANKL表达达到顶峰，出现大面积玻璃样变区域，OPG在加力后第10天表达达到顶峰；D组中RANKL与OPG表达趋势变化与C组一致，在第7、10天时表达量均小于C组，大量玻璃样变区域在第10天中出现。结论　坏死性凋亡在正畸牙齿移动某一过程中可以促进牙齿移动，Nec-1减少牙周组织中RANKL与OPG表达，抑制破骨细胞分化成熟，阻碍牙齿移动。

关键词: 关键词：牙齿移动, 玻璃样变, 坏死性凋亡, Necrostatin-1

Abstract: Abstract：　Objective　To investigate that necroptosis has effects on distance and receptor activator of nuclear factor-κB ligand(RANKL), osteoprotegerin(OPG) expression changes in periodontal tissues during tooth movement in rats. Methods　The orthodontic model of maxillary tooth movement was established in rats, and according to the use of necroptosis inhibitor Necrostatin-1 (Nec-1), the rats were randomly divided into control group (group A), inhibitor group (group B), activation group (group C) and activation + inhibitor group (group D). The forward movement distance of the maxillary left first molar was measured with the vernier caliper, the hyalinization was observed by HE staining on the pressure side, the expression of RANKL and OPG in the periodontal tissue of the pressure side was detected by immunohistochemistry on the 1st, 3rd, 7th, 10th and 14th day. Results　In the group A and group B, the distances of teeth movement and the area of hyalinization did not change appeared, the expression of RANKL and OPG was less. In the group C and group D, the distances of tooth movement change appeared, there was significant difference between the two groups on the 3rd, 7th, 10th and 14th day(P<0.05); Moreover, the expression of RANKL reached the peak at 7 days, the large areas of hyalinization change appeared at the same time, and the expression of OPG reached the peak at 10 days in group C; The expression trend of RANKL and OPG in the group D was the same as that in the group C, but the expression level in group D was less than that in the group C on the 7th and 10th day, and the range of hyalinization change appeared on the 10th day. Conclusion　Necroptosis can promote tooth movement during orthodontic tooth movement. Nec-1 reduced the expression of RANKL and OPG, inhibited the differentiation and maturation of osteoclasts and hindered tooth movement.

Key words: Key words: tooth movement, hyalinization, necroptosis, Necrostatin-1

季开心陈思言张敏杰张苗苗. 坏死性凋亡在大鼠牙移动过程中对牙周组织改建的影响[J]. 口腔医学, 2021, 41(12): 1068-1072.

参考文献 1崔

1崔

淑霞,常悦,卫晓霞.正畸力对牙周病大鼠牙槽骨改建影响的实验研究[J].河南医学研究,2017,26(06):967-969.2 Li C, Chung CJ, Hwang CJ, Lee KJ. Local injection of RANKL facilitates tooth movement and alveolar bone remodelling. [J]. Oral Dis. 2019,25(2):550-560.3 Honma M, Ikebuchi Y, Suzuki H. Mechanisms of RANKL delivery to the osteoclast precursor cell surface. [J]. J Bone Miner Metab. 2021,39(1):27-33.4 Shlomovitz I, Zargarian S, Erlich Z, Edry-Botzer L, Gerlic M. Distinguishing Necroptosis from Apoptosis. [J]. Methods Mol Biol. 2018,1857:35-51.5 Chen J, Kos R, Garssen J, Redegeld F. Molecular Insights into the Mechanism of Necroptosis: The Necrosome As a Potential Therapeutic Target. [J]. Cells. 2019,21;8(12):1486.6 Linkermann A, Green DR: Necroptosis. [J]. N Engl J Med 2014, 370:455-465.7 Zhuang C, Chen F. Small-Molecule Inhibitors of Necroptosis: Current Status and Perspectives. [J]. J Med Chem. 2020, 27;63(4):1490-1510. 8 Xu J, Zhao X, Zeng J, Yu JH, Guan S, Xu XM, Mei L. Role of autophagy in the periodontal ligament reconstruction during orthodontic tooth movement in rats. [J].J Dent Sci. 2020,15(3):351-363.9 Buczko P, Pawlak D, Kasacka I. An important pathway of apoptotic effect of nickel early released from orthodontic appliances - Preliminary data. [J]. Pharmacol Rep. 2018,70(4):766-768.10 Pasparakis M, Vandenabeele P. Necroptosis and its role in inflammation. [J]. Nature. 2015，15;517(7534):311-20.11 Degterev A, Huang Z, Boyce M, Li Y, Jagtap P, Mizushima N, Cuny GD, Mitchison TJ, Moskowitz MA, Yuan J. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. [J]. Nat Chem Biol. 2005,1(2):112-9. 12 Laurien L, Nagata M, Schünke H, Delanghe T, Wiederstein JL, Kumari S, Schwarzer R, Corona T, Krüger M, Bertrand MJM, Kondylis V, Pasparakis M. Autophosphorylation at serine 166 regulates RIP kinase 1-mediated cell death and inflammation. [J]. Nat Commun. 2020，8;11(1):1747.13. Xie T, Peng W, Liu Y, Yan C, Maki J, Degterev A, Yuan J, Shi Y. Structural basis of RIP1 inhibition by necrostatins. Structure. 2013, 5;21(3):493-9.14 Shlomovitz I, Zargarian S, Erlich Z, Edry-Botzer L, Gerlic M. Distinguishing Necroptosis from Apoptosis. [J]. Methods Mol Biol. 2018;1857:35-51.15 Welz PS, Wullaert A, Vlantis K, Kondylis V, Fernández-Majada V, Ermolaeva M, Kirsch P, Sterner-Kock A, van Loo G, Pasparakis M. FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation. [J]. Nature. 2011,31;477(7364):330-4. 16 Zhu X, Chan YT, Yung PSH, Tuan RS, Jiang Y. Subchondral Bone Remodeling: A Therapeutic Target for Osteoarthritis. [J]. Front Cell Dev Biol. 2021,21;8:607764. 17 Aoki S, Honma M, Kariya Y, Nakamichi Y, Ninomiya T, Takahashi N, Udagawa N, Suzuki H. Function of OPG as a traffic regulator for RANKL is crucial for controlled osteoclastogenesis.[J]. J Bone Miner Res. 2010,25(9):1907-21.18 Noguchi T, Kitaura H, Ogawa S, Qi J, Shen WR, Ohori F, Marahleh A, Nara Y, Pramusita A, Mizoguchi I. TNF-α stimulates the expression of RANK during orthodontic tooth movement. [J]. Arch Oral Biol. 2020,17:104796.19 Cui H, Zhu Y, Yang Q, Zhao W, Zhang S, Zhou A, Jiang D. Necrostatin-1 treatment inhibits osteocyte necroptosis and trabecular deterioration in ovariectomized rats. [J]. Sci Rep. 2016,5;6:33803.