口腔医学研究

口腔医学研究 ›› 2023, Vol. 39 ›› Issue (2): 118-123.DOI: 10.13701/j.cnki.kqyxyj.2023.02.006

• 口腔正畸学研究 • 上一篇    下一篇

重组人转化生长因子-β1对大鼠正畸牙移动模型成骨细胞分化及ERK/MAPK信号通路的影响

林维龙1, 吴晓沛2, 何薇薇1, 安峰1*   

  1. 1.河北北方学院附属第一医院口腔科 河北 张家口 075000;
    2.张家口学院 医学院口腔医学教研室 河北 张家口 075000
  • 收稿日期:2022-05-15 出版日期:2023-02-28 发布日期:2023-02-20
  • 通讯作者: * 安峰,E-mail:80562603@qq.com
  • 作者简介:林维龙(1981~ ),男,辽宁海城人,硕士,主治医师,主要从事口腔正畸学研究工作。
  • 基金资助:
    河北省医学科学研究课题计划项目(编号:20200506)

Effects of Recombinant Human Transforming Growth Factor-β1 on Osteoblast Differentiation and ERK/MAPK Signaling Pathway in Orthodontic Tooth Movement Model of Rats

LIN Weilong1, WU Xiaopei2, HE Weiwei1, AN Feng1*   

  1. 1. Department of Stomatology, the First Hospital Affiliated to Hebei North University, Zhangjiakou 075000, China;
    2. Department of Stomatology, Medical College, Zhangjiakou University, Zhangjiakou 075000, China
  • Received:2022-05-15 Online:2023-02-28 Published:2023-02-20

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摘要： 目的: 探讨重组人转化生长因子-β1(rhTGF-β1)对大鼠正畸牙移动模型细胞外信号调节激酶(ERK)/丝裂原活化蛋白激酶(MAPK)信号通路及成骨细胞分化的影响。方法: 将SD大鼠随机分为:对照组、模型组、rhTGF-β1低剂量组、rhTGF-β1中剂量组、rhTGF-β1高剂量组。模型组、rhTGF-β1低、中、高剂量组建立大鼠正畸牙移动模型,各组从造模第1天开始给药,rhTGF-β1(低、中、高)剂量组于双侧上颌第一磨牙近中牙龈黏膜下分别注射1.25、2.5、5 ng/mL的rhTGF-β1溶液0.1 mL,对照组注射0.1 mL生理盐水,每2 d给药1次,持续14 d。游标卡尺测量大鼠上颌第一磨牙移动距离;苏木精-伊红染色观察大鼠牙周及牙槽骨组织病理形态;酶联免疫吸附法检测血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、骨保护素(OPG)、核因子κB受体活化因子配体(RANKL)水平;Western blot检测大鼠牙周及牙槽骨组织成骨相关蛋白[骨钙素(OCN)、骨桥蛋白(OPN)、Runt相关转录因子2(Runx2)]和ERK/MAPK通路相关蛋白表达。结果: 与对照组相比,模型组大鼠牙张力侧牙周组织膜纤维拉伸变长,组织间隙变宽,基质增生,成骨细胞数量大量减少近乎消失,呈现病理损伤,上颌第一磨牙移动距离、血清TNF-α、IL-6、RANKL、牙周及牙槽骨组织p-ERK1/2/ERK1/2、p-p38 MAPK/p38 MAPK蛋白表达水平明显升高,血清OPG、牙周及牙槽骨组织OCN、OPN、Runx2蛋白表达水平明显降低(P＜0.05);与模型组相比,rhTGF-β1低、中、高剂量组大鼠牙张力侧牙周及牙槽骨组织病理损伤逐步减轻,血清TNF-α、IL-6、RANKL、牙周及牙槽骨组织p-ERK1/2/ERK1/2、p-p38 MAPK/p38 MAPK蛋白表达水平依次降低,上颌第一磨牙移动距离、血清OPG、牙周及牙槽骨组织OCN、OPN、Runx2蛋白表达水平依次升高(P＜0.05),且各组之间呈剂量依赖性。结论: rhTGF-β1可减轻大鼠正畸牙移动模型炎症反应,促使成骨分化,加速正畸牙移动,可能与抑制ERK/MAPK信号通路激活有关。

关键词: 重组人转化生长因子-β1, 大鼠正畸牙移动模型, ERK/MAPK信号通路, 成骨细胞分化

Abstract: Objective: To investigate the effects of recombinant human transforming growth factor-β1 (rhTGF-β1) on ERK/MAPK signaling pathway and osteoblast differentiation in orthodontic tooth movement model of rats. Methods: SD rats were randomly divided into control group, model group, rhTGF-β1 low dose group, rhTGF-β1 medium dose group, and rhTGF-β1 high dose group. Orthodontic tooth movement models of rats were established in model group, and rhTGF-β1 low, medium, and high dose groups. Each group was given drugs from the first day of modeling, the rhTGF-β1 (low, medium, and high) dose groups were injected with 0.1 mL of 1.25, 2.5, and 5 ng/mL rhTGF-β1 solution under the mesial gingival mucosa of bilateral maxillary first molars, respectively, and the control group was injected with 0.1 mL normal saline, once every 2 days for 14 days. The movement distance of the rat maxillary first molar was measured. The pathological morphology of periodontal and alveolar bone were observed in rats. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), osteoprotegerin (OPG), and receptor activator of nuclear factor-κB ligand (RANKL) were detected. The expressions of osteogenic related proteins [osteocalcin (OCN), osteopontin (OPN), runt related transcription factor 2 (Runx2)], and ERK/MAPK pathway related proteins in rat periodontal and alveolar bone tissues were detected by Western blot. Results: Compared with those in the control group, the tensile fiber of periodontal tissue in the tension side of rat teeth in the model group was elongated, the tissue gap was widened, the matrix was proliferated, and the number osteoblasts decreased and almost disappeared, showing pathological damage, the movement distance of the maxillary first molar, serum TNF-α, IL-6, RANKL, p-ERK1/2/ERK1/2, and p-p38 MAPK/p38 MAPK protein expression levels in periodontal and alveolar bone tissues were significantly increased, and serum OPG, expression levels of OCN, OPN, and Runx2 protein in periodontal and alveolar bone tissues were significantly decreased (P<0.05). Compared with those in the model group, the pathological damage of periodontal and alveolar bone in the tension side of rats teeth in the rhTGF-β1 low, medium, and high dose groups was gradually reduced, serum TNF-α, IL-6, RANKL, p-ERK1/2/ERK1/2, and p-p38 MAPK/p38 MAPK protein expression levels in periodontal and alveolar bone tissues were decreased in turn, the movement distance of the maxillary first molar, serum OPG, expression levels of OCN, OPN, and Runx2 protein in periodontal and alveolar bone tissues were significantly increased in turn (P<0.05), there was a dose-dependent relationship between the groups. Conclusion: rhTGF-β1 can reduce the inflammatory reaction of rat orthodontic tooth movement model, promote osteogenic differentiation, and accelerate orthodontic tooth movement, which may be related to inhibiting the activation of ERK/MAPK signal pathway.

Key words: recombinant human transforming growth factor-β1, orthodontic tooth movement model in rats, ERK/MAPK signal pathway, osteoblasts differentiation