正畸牙齿移动过程中Noggin在牙周组织中表达的动物实验研究
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摘要
目的:Noggin是骨形态发生蛋白(BMPs)信号传导通路上的细胞外拮抗剂。Noggin通过与细胞表面的BMPs受体相竞争,特异性的与BMPs结合,阻碍BMPs与其自身受体结合及下游区的信号传导从而拮抗BMPs的成骨作用。本实验的主要目的为探究在大鼠正畸牙齿移动过程中,Noggin在牙周组织中的表达情况,拟探讨Noggin与正畸牙齿移动的关系及其在牙齿移动过程中的作用。
方法:选取8周龄SD大鼠,雄性,体重范围在180～220g,共21只,每3只为一组,随机分为7组。建立正畸牙齿移动模型,以大鼠上颌左侧牙弓为实验侧,右侧为对照侧。本实验支抗选择正畸专用微螺钉种植体,近中牵引力由镍钛拉簧提供,力量大小约为40g,以使上颌实验侧第一磨牙向近中移动;对照侧不做任何处理。依据实验分组情况,分别在实验的第1天、3天、5天、7天、14天、21天、28天各个时间点进行心脏灌流处死大鼠,取大鼠上颌两侧磨牙和周围组织作为标本并制备切片,进行苏木素-伊红(HE)染色并采用免疫组织化学方法,检测实验性大鼠正畸牙齿移动过程中Noggin在牙周组织中的表达变化,用计算机分析软件进行灰度值的测量,统计学分析采用SPSS 17.0统计分析软件进行。
结果:实验结果显示,在大鼠正畸牙齿移动过程中,Noggin在牙周组织中的表达和分布情况随着加力时间的变化,呈现特异性的分布模式。灰度值分析显示,牙周组织中Noggin的表达水平在第7天组最强,到第28天组便基本接近对照组的水平。
结论:Noggin在牙周组织中的阳性表达,说明了Noggin与大鼠正畸牙齿移动的牙周组织改建过程有关。作为骨形态发生蛋白(BMPs)的拮抗剂,Noggin的表达与BMPs的表达相伴随。本实验揭示了Noggin在牙周组织中的表达和分布情况,提示Noggin在限制BMPs过度表达过程中可能发挥重要的作用。
Objective: Noggin is an extracellar antagonist of BMPs’signaling. Noggin acts by binding BMPs, thus preventing them from binding to their receptors and subsequently blocking the actions of BMPs.The main purpose of this study is to examine the expression of Noggin in periodontal tissues during orthodontic tooth movement in rats.
Method: Selected 21 8-week-old male SD rat(180-220g),which were randomly divided into 7 groups. Established orthodontic tooth movement model and chose the left side of the maxillary as the experimental side. The right side was taken as control side. The mini-implant was used as the anchorage part. A coil spring was placed between the maxillary first molar and mini-implant. The first molar was moved mesially by about 40g force. Rats were killed after 1,3,5,7,14 ,21,28 days. The tissue was stained with HE to observe the histological changes of periodontal tissues. Immunohistochemical assay was used to determine Noggin levels. And the result was analyzed by statistic test.
Results:Noggin has a specific temporal and spatial expression profiles during the orthodontic tooth movement. The expression of Noggin was clearly upregulated in the early phase and then decreased thereafter.It reached the peak on 7 day,then decreased gradually ,the expression is almost equal to the control group on 28 day group.
Conclusion:Noggin involved in the rat bone remodeling and orthodontic tooth movement, and played a very important role.As an antagonist,noggin often is expressed in conjunction with BMPs,conceivably defining boundaries of BMP induced structures.The upregulation of the Noggin expression points to the possibility of a negative feedback mechanism for BMPs induced bone formation.
方法:选取8周龄SD大鼠,雄性,体重范围在180～220g,共21只,每3只为一组,随机分为7组。建立正畸牙齿移动模型,以大鼠上颌左侧牙弓为实验侧,右侧为对照侧。本实验支抗选择正畸专用微螺钉种植体,近中牵引力由镍钛拉簧提供,力量大小约为40g,以使上颌实验侧第一磨牙向近中移动;对照侧不做任何处理。依据实验分组情况,分别在实验的第1天、3天、5天、7天、14天、21天、28天各个时间点进行心脏灌流处死大鼠,取大鼠上颌两侧磨牙和周围组织作为标本并制备切片,进行苏木素-伊红(HE)染色并采用免疫组织化学方法,检测实验性大鼠正畸牙齿移动过程中Noggin在牙周组织中的表达变化,用计算机分析软件进行灰度值的测量,统计学分析采用SPSS 17.0统计分析软件进行。
结果:实验结果显示,在大鼠正畸牙齿移动过程中,Noggin在牙周组织中的表达和分布情况随着加力时间的变化,呈现特异性的分布模式。灰度值分析显示,牙周组织中Noggin的表达水平在第7天组最强,到第28天组便基本接近对照组的水平。
结论:Noggin在牙周组织中的阳性表达,说明了Noggin与大鼠正畸牙齿移动的牙周组织改建过程有关。作为骨形态发生蛋白(BMPs)的拮抗剂,Noggin的表达与BMPs的表达相伴随。本实验揭示了Noggin在牙周组织中的表达和分布情况,提示Noggin在限制BMPs过度表达过程中可能发挥重要的作用。
Objective: Noggin is an extracellar antagonist of BMPs’signaling. Noggin acts by binding BMPs, thus preventing them from binding to their receptors and subsequently blocking the actions of BMPs.The main purpose of this study is to examine the expression of Noggin in periodontal tissues during orthodontic tooth movement in rats.
Method: Selected 21 8-week-old male SD rat(180-220g),which were randomly divided into 7 groups. Established orthodontic tooth movement model and chose the left side of the maxillary as the experimental side. The right side was taken as control side. The mini-implant was used as the anchorage part. A coil spring was placed between the maxillary first molar and mini-implant. The first molar was moved mesially by about 40g force. Rats were killed after 1,3,5,7,14 ,21,28 days. The tissue was stained with HE to observe the histological changes of periodontal tissues. Immunohistochemical assay was used to determine Noggin levels. And the result was analyzed by statistic test.
Results:Noggin has a specific temporal and spatial expression profiles during the orthodontic tooth movement. The expression of Noggin was clearly upregulated in the early phase and then decreased thereafter.It reached the peak on 7 day,then decreased gradually ,the expression is almost equal to the control group on 28 day group.
Conclusion:Noggin involved in the rat bone remodeling and orthodontic tooth movement, and played a very important role.As an antagonist,noggin often is expressed in conjunction with BMPs,conceivably defining boundaries of BMP induced structures.The upregulation of the Noggin expression points to the possibility of a negative feedback mechanism for BMPs induced bone formation.
引文
1.Abe E,Yamamoto M,Taguchi Y,et al.Essential requirement of BMPs-2/4 for both osteoblast and osteoclast formation in murine bone marrow cultures from adult mice: antagonism by noggin[J].J Bone Miner Res,2000,15(4):663-673.
2.Smith WC, Harland RM. Expression cloning of Noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos[J]. Cell,1992,70:829- 840.
3.zimmerman LB,De Jesus-Escobar JM,Harlald RM.The Spemann organizer signal Noggin binds and inactivates bone morphogenetic protein 4[J].Cell,1996,86(4):599～606.
4.Zehentner BK,Haussnmnn A,Burtseher H.The bone morphogenetic proteinantagonist Noggin is regulated by Sox9 during endochondral differentiation[J].Growth Differ,2002,44(1):1—9.
5.Gazzerro E,Gangji V,Canalis E.Bone morphogenetic proteins induce the expression of noggin,which limits their activity in cultured rat osteoblasts[J].J Clin Invest,1998,102(12):2106—2114.
6.Devlin RD,Du Z,Pereira RC,et a1.Skeletal overexpression of noggin results in osteopenia and reduced bone formation[J].Endocrinology,2003,144(5):1972—1978.
7.Wan DC,Pomerantz JH,Brunet LJ,et a1.Noggin suppression enhances in vitro osteogenesis and accelerates in vivo bone formation[J].J Biol Chem,2007, 282(36):26450-26459.
8.杨琳琳。正畸牙齿移动过程中BMP-2在牙周组织中表达的动物实验研究[D]。大连医科大学,2010.
9.Kanomi R.Mini-implant for orthodontic anchorage[J].J Clin Orthod,1997,31(11):763-767.
10.傅民魁主编.口腔正畸学[M].第5版.北京:人民卫生出版社.2007,173-181.
11.Melsen B, Costa A. Immediate loading of implants used for orthodontic anchorage[J].Clin Orthod Res,2000,3(1) :23-28.
12.Kyung HM,Park HS,Bae SM.Development of orthodontic micro-implants for intraoral anchorage[J].J Clin Orthod,2003,37:321-8.
13.张月兰,曹选平,崔淑霞,等。即刻负载后微螺钉支抗种植体稳定性的实验研究[J]。中国口腔种植学杂志,2009, 14( 1) : 5 - 7.
14.Valenzuela DM,Economides AN,Rojas E,et al.Identification of mammalian Noggin and its expression in the adult nervous system[J].J Neurosci,1995,15(9):6077-84.
15.Bachiller D,Klingensmith J,Kemp C,et al.The organizer factors Chordin and Noggin are required for mouse forebrain development[J].Nature,2000,403(6770):658 - 661.
16.Brunet LJ,McMahon JA,McMahon AP,et al.Noggin,cartilage morphogenesis,and joint formation in the mammalianskeleton[J].Science,1998,280(5368):1455-1457.
17.Warren SM,Brunet LJ,Harland RM,et al.The BMP antagonist noggin regulates cranial suture fusion[J].Nature, 2003,422(6932):625-9.
18.Botchkarev VA ,Botchkareva NV ,Nakamura M,et al . Noggin is required for induction of the hair follicle growth phase in postnatal skin [ J ] .FASEB J ,2001 ,15 (12) :2205～2214.
19.Allen SP,Bogandi JP,Barlow AJ,et al.Misexpression of Noggin leads to septal defects in the outflow tract of the chick heart [J].Dev Biol,2001,235(1):98～100.
20.Leboy PS.Regulating bone growth and development with bone morphogenetic proteins[J].Am J Pathol,2006,1068(4):14-18.
21.Nohe A ,Keating E,Knaus P ,et al. Signal transduction of bone morphogenetic protein receptors[J] .Cell Signal ,2004,16(3):291-299.
22.Aspenberg P, Jeppsson C, Economides AN .The bone morphogenetic proteins antagonist noggin inhibits membranous ossification[J]. J Bone Miner Res,2001, 16(3):497–500.
23.傅民魁主编。口腔正畸专科教程,人民卫生出版社2007年10月第一版,第一篇基本理论篇,第八章正畸牙齿移动的生物学基础,123一124页。
24.杨彤彤,米宇菁.大鼠实验性牙齿移动过程中骨形成蛋白2的表达和意义[J].山西医药杂志, 2005,34(10):824-826.
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2.Smith WC, Harland RM. Expression cloning of Noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos[J]. Cell,1992,70:829- 840.
3.zimmerman LB,De Jesus-Escobar JM,Harlald RM.The Spemann organizer signal Noggin binds and inactivates bone morphogenetic protein 4[J].Cell,1996,86(4):599～606.
4.Zehentner BK,Haussnmnn A,Burtseher H.The bone morphogenetic proteinantagonist Noggin is regulated by Sox9 during endochondral differentiation[J].Growth Differ,2002,44(1):1—9.
5.Gazzerro E,Gangji V,Canalis E.Bone morphogenetic proteins induce the expression of noggin,which limits their activity in cultured rat osteoblasts[J].J Clin Invest,1998,102(12):2106—2114.
6.Devlin RD,Du Z,Pereira RC,et a1.Skeletal overexpression of noggin results in osteopenia and reduced bone formation[J].Endocrinology,2003,144(5):1972—1978.
7.Wan DC,Pomerantz JH,Brunet LJ,et a1.Noggin suppression enhances in vitro osteogenesis and accelerates in vivo bone formation[J].J Biol Chem,2007, 282(36):26450-26459.
8.杨琳琳。正畸牙齿移动过程中BMP-2在牙周组织中表达的动物实验研究[D]。大连医科大学,2010.
9.Kanomi R.Mini-implant for orthodontic anchorage[J].J Clin Orthod,1997,31(11):763-767.
10.傅民魁主编.口腔正畸学[M].第5版.北京:人民卫生出版社.2007,173-181.
11.Melsen B, Costa A. Immediate loading of implants used for orthodontic anchorage[J].Clin Orthod Res,2000,3(1) :23-28.
12.Kyung HM,Park HS,Bae SM.Development of orthodontic micro-implants for intraoral anchorage[J].J Clin Orthod,2003,37:321-8.
13.张月兰,曹选平,崔淑霞,等。即刻负载后微螺钉支抗种植体稳定性的实验研究[J]。中国口腔种植学杂志,2009, 14( 1) : 5 - 7.
14.Valenzuela DM,Economides AN,Rojas E,et al.Identification of mammalian Noggin and its expression in the adult nervous system[J].J Neurosci,1995,15(9):6077-84.
15.Bachiller D,Klingensmith J,Kemp C,et al.The organizer factors Chordin and Noggin are required for mouse forebrain development[J].Nature,2000,403(6770):658 - 661.
16.Brunet LJ,McMahon JA,McMahon AP,et al.Noggin,cartilage morphogenesis,and joint formation in the mammalianskeleton[J].Science,1998,280(5368):1455-1457.
17.Warren SM,Brunet LJ,Harland RM,et al.The BMP antagonist noggin regulates cranial suture fusion[J].Nature, 2003,422(6932):625-9.
18.Botchkarev VA ,Botchkareva NV ,Nakamura M,et al . Noggin is required for induction of the hair follicle growth phase in postnatal skin [ J ] .FASEB J ,2001 ,15 (12) :2205～2214.
19.Allen SP,Bogandi JP,Barlow AJ,et al.Misexpression of Noggin leads to septal defects in the outflow tract of the chick heart [J].Dev Biol,2001,235(1):98～100.
20.Leboy PS.Regulating bone growth and development with bone morphogenetic proteins[J].Am J Pathol,2006,1068(4):14-18.
21.Nohe A ,Keating E,Knaus P ,et al. Signal transduction of bone morphogenetic protein receptors[J] .Cell Signal ,2004,16(3):291-299.
22.Aspenberg P, Jeppsson C, Economides AN .The bone morphogenetic proteins antagonist noggin inhibits membranous ossification[J]. J Bone Miner Res,2001, 16(3):497–500.
23.傅民魁主编。口腔正畸专科教程,人民卫生出版社2007年10月第一版,第一篇基本理论篇,第八章正畸牙齿移动的生物学基础,123一124页。
24.杨彤彤,米宇菁.大鼠实验性牙齿移动过程中骨形成蛋白2的表达和意义[J].山西医药杂志, 2005,34(10):824-826.
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