rhTGF-β1介导BMP2/Smad1通路对正畸牙移动大鼠破骨细胞形成的影响OA
Effect of rhTGF-β1 on Osteoclast Formation via the BMP2/Smad1 Pathway in Rats during Orthodontic Tooth Movement
目的 基于大鼠骨形态发生蛋白 2(bone morphogenetic protein2,BMP2)/Smad家族成员 1(smad family member 1,Smad1)通路,探究重组人转化生长因子-β1(recombinant human transforming growth factor-β1,rhTGF-β1)对正畸牙移动(orthodontic tooth movement,OMT)大鼠破骨细胞形成的影响.方法 构建大鼠OTM模型,采用显微CT(Micro-CT)分析测定OTM的距离;通过抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase,TRAP)染色评估压力侧破骨细胞活性;苏木精-伊红(hematoxylin and eosin,HE)染色评估压力侧组织形态学特征,免疫组化(immunohistochemistry,IHC)染色和蛋白质印迹(Western blot)测定相关蛋白表达水平.结果 与正常组相比,Model组大鼠OTM距离增加(P<0.01),牙周间隙明显变窄并出现吸收陷窝,压力侧的基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)、核因子κB受体活化因子配体(receptor activator of nuclear factor kappa B ligand,RANKL)增加(P<0.01)、骨保护素(osteoprotegerin,OPG)表达降低(P<0.01),BMP2/Smad1 信号通路被激活(P<0.01).经BMP2 抑制剂Noggin处理后,与Model组相比,BMP2、p-Smad1 表达显著降低(P<0.01),OTM距离显著降低(P<0.01),且压力侧的TRAP、MMP-9 及RANKL表达均显著降低(P<0.01),OPG升高(P<0.01).经rhTGF-β1 处理的大鼠中,较Model组OTM距离显著增加(P<0.01),TRAP阳性多核细胞数量升高(P<0.01),压力侧的MMP-9 及RANKL表达均显著升高(P<0.05)、OPG表达显著降低(P<0.01),且BMP2、p-Smad1 表达上调(P<0.01).此外,rhTGF-β1+Noggin组部分逆转了rhTGF-β1 组大鼠的破骨细胞数量的增加效应(P<0.01).结论 正畸力可促进破骨细胞形成,且rhTGF-β1 可通过BMP2/Smad1 信号通路增强OTM过程中破骨细胞的形成.
Objective To investigate the effect of recombinant human transforming growth factor-β1(rhTGF-β1)on osteoclast formation during orthodontic tooth movement(OTM)in rats,based on the bone morphogenetic protein 2(BMP2)/smad family member 1(Smad1)pathway.Methods The rat OTM model was established,and the distance of OTM was measured using micro-computed tomography(Micro-CT)analysis.T artrate-resistant acid phosphatase(TRAP)staining was performed to assess osteoclast activity on the pressure side.Hematoxylin and eosin(HE)staining was used to evaluate histomorphological characteristics on the pressure side.Immunohistochemistry(IHC)and Western blot analysis were conducted to determine the protein expression levels of related markers.Results Compared with the normal group,the OTM distance was increased in the Model group(P<0.01),the periodontal ligament space was significantly narrowed with the presence of resorption lacunae,the expression of matrix metalloproteinase-9(MMP-9)and receptor activator of nuclear factor kappa B ligand(RANKL)on the pressure side was increased(P<0.01),the expression of osteoprotegerin(OPG)was decreased(P<0.01),and the BMP2/Smad1 signaling pathway was activated(P<0.01).The differences were statistically significant(P<0.01).After Noggin treatment to inhibit BMP2,compared with the Model group,the expression of BMP2 and p-Smad1 was significantly decreased(P<0.01),the OTM distance was significantly reduced(P<0.01),and the expression of TRAP,MMP-9,and RANKL on the pressure side was significantly decreased while OPG was increased(P<0.01).In rats treated with rhTGF-β1,compared with the Model group,the OTM distance was significantly increased(P<0.01),the number of TRAP-positive multinucleated cells was higher(P<0.01),the expression of MMP-9,and RANKL on the pressure side was significantly increased(P<0.01),OPG expression was significantly decreased(P<0.01),and the expression of BMP2 and p-Smad1 was up-regulated(P<0.01).Furthermore,the rhTGF-β1+Noggin group partially reversed the increase in osteoclast number induced by rhTGF-β1 alone(P<0.01).Conclusion Orthodontic force can promote osteoclast formation,and rhTGF-β1 can increase osteoclast formation during OTM via the BMP2/Smad1 signaling pathway.
娄会杰;李培培;樊哲
唐山职业技术学院附属医院口腔正畸科,河北 唐山 063000唐山职业技术学院附属医院口腔正畸科,河北 唐山 063000唐山职业技术学院附属医院正畸科,河北 唐山 063000
医药卫生
rhTGF-β1BMP2/Smad1通路正畸牙移动破骨细胞
rhTGF-β1BMP2/Smad1 pathwayorthodontic tooth movementosteoclast
《昆明医科大学学报》 2026 (1)
23-30,8
河北省医学科学研究课题计划资助(20231812)
评论