FGFR2功能增强对小鼠下颌骨髁突发育影响

doi:10.16288/j.yczz.14-370

遗传 ›› 2015, Vol. 37 ›› Issue (6): 561-567.doi: 10.16288/j.yczz.14-370

FGFR2功能增强对小鼠下颌骨髁突发育影响

梁鑫¹, 张波², 刘苹², 翁土军², 张莉², 贺龙珠¹, 李芳菲², 屈晨¹, 王萍¹

1. 重庆医科大学附属第一医院口腔科,重庆 400016;
2. 第三军医大学大坪医院野战外科研究所第四研究室,重庆 400042

收稿日期:2014-10-28 修回日期:2015-01-20 出版日期:2015-06-20 发布日期:2015-03-12
通讯作者: 王萍,博士,教授,研究方向：牙髓根尖周病、口腔颅颌面组织生长发育研究。E-mail: cqcnwp@sina.com
作者简介:梁鑫,硕士,专业方向：口腔内科学。E-mail: 654066262@qq.com
基金资助:
国家重点基础研究发展规划项目(973计划)(编号：2011CB964701)资助

A gain-of-function mutation in FGFR2 influences mandibular condylar development on mice

Xin Liang¹, Bo Zhang², Ping Liu², Tujun Weng², Li Zhang², Longzhu He¹, Fangfei Li², Chen Qu¹, Ping Wang¹

1. Department of Stomatology, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China;
2. Department 4, Daping Hospital, Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China

Received:2014-10-28 Revised:2015-01-20 Online:2015-06-20 Published:2015-03-12

摘要/Abstract

摘要： 成纤维细胞生长因子受体2(Fibroblast growth factor receptor, FGFR2)是参与调控骨骼发育的重要分子,在调控软骨内成骨过程中发挥着重要作用。为了探讨FGFR2功能增强对小鼠下颌骨髁突生长发育的影响,文章以FGFR2功能增强型点突变(Fgfr2^+/S252W)小鼠为研究对象,采用番红固绿染色研究Fgfr2^+/S252W小鼠下颌骨髁突不同生长发育阶段的组织形态;利用免疫细胞化学染色和实时荧光定量PCR方法检测X型胶原(Col X)在3周龄小鼠髁突肥大软骨细胞中的表达。结果显示,1周龄、3周龄和6周龄突变型小鼠下颌骨髁突的软骨细胞层宽度都比同窝野生型窄,钙化软骨细胞层退化时间早,骨小梁钙化绿染程度深;Col X在突变型小鼠下颌骨髁突的表达高于同窝野生型小鼠(P<0.001)。结果表明,FGFR2功能增强可导致小鼠下颌骨髁突软骨层组织形态异常,抑制髁突软骨内成骨,从而导致下颌骨髁突发育畸形。

关键词: 下颌骨, 髁突, 成纤维细胞生长因子受体2

Abstract: The development of the skeleton is regulated by numerous signaling molecules expressed in epiphyseal cartilage controlling both chondrogenesis and osteogenesis such as fibroblast growth factor receptors (FGFRs). In order to explore the important effect of fibroblast growth factor receptor 2 (FGFR2) in the process of mandibular condylar growth, we introduced gain-of-function Fgfr2^+/S252W mice, and investigated mandibular condylar morphology by means of safranin-o/fast green staining at the stage of 1 week, 3 weeks and 6 weeks. The mutant mice displayed narrower width of the mandibular condylar growth plate, stronger stainings of trabecular bone at the stage of 1 week, 3 weeks and 6 weeks and faster degradation of the calcified cartilage cell layer at the stage of 6 weeks. We also assessed the expression of type X collagen (Col X) in mandibular condyle at the stage of 3 weeks by immunohistochemical staining and real-time PCR. The results showed that Col X was increased in the mutant mice. In conclusion, the gain-of-function mutation in FGFR2 resulted in histopathological abnormalities and development deformity of mandibular condyle cartilage in mice, which inhibited endochondral bone formation.

Key words: mandibular, condyle, fibroblast growth factor receptor 2

梁鑫, 张波, 刘苹, 翁土军, 张莉, 贺龙珠, 李芳菲, 屈晨, 王萍. FGFR2功能增强对小鼠下颌骨髁突发育影响[J]. 遗传, 2015, 37(6): 561-567.

Xin Liang, Bo Zhang, Ping Liu, Tujun Weng, Li Zhang, Longzhu He, Fangfei Li, Chen Qu, Ping Wang. A gain-of-function mutation in FGFR2 influences mandibular condylar development on mice[J]. HEREDITAS(Beijing), 2015, 37(6): 561-567.

参考文献

[1] Martín AE, del R Pani M, Holgado NR, López Miranda LI, Meheris HE, Garat JA. Facial development disorders due to inhibition to endochondral ossification of mandibular condyle process caused by malnutrition. Angle Orthod , 2014, 84(3): 473-478.
[2] Xie YL, Zhou SR, Chen HG, Du XL, Chen L. Recent research on the growth plate: Advances in fibroblast growth factor signaling in growth plate development and disorders. J Mol Endocrinol , 2014, 53(1): T11-T34.
[3] Itoh N, Ornitz DM. Evolution of the Fgf and Fgfr gene families. Trends Genet , 2004, 20(11): 563-569.
[4] Lajeunie E, Cameron R, El Ghouzzi V, De Parseval N, Journeau P, Gonzales M, Delezoide AL, Bonaventure J, Le Merrer M, Renier D. Clinical variability in patients with Apert’s syndrome. J Neurosurg , 1999, 90(3): 443-447.
[5] Yu K, Ornitz DM. Uncoupling fibroblast growth factor receptor 2 ligand binding specificity leads to Apert syndrome-likephenotypes. Proc Natl Acad Sci USA , 2001, 98(7): 3641-3643.
[6] Wang YL, Xiao R, Yang F, Karim BO, Iacovelli AJ, Cai JL, Lerner CP, Richtsmeier JT, Leszl JM, Hill CA, Yu K, Ornitz DM, Elisseeff J, Huso DL, Jabs EW. Abnormalities in cartilage and bone development in the Apert syndrome FGFR2 +/S252W mouse. Development , 2005, 132(15): 3537- 3548.
[7] Chen L, Li D, Li CL, Engel A, Deng CX. A Ser 252 Trp substitution in mouse fibroblast growth factor receptor 2(Fgfr2) result in craniosynostosis. Bone , 2003, 33(2): 169-178.
[8] Kronenbcrg HM. Developmental regulation of the growth plate. Nature , 2003, 423(6937): 332-336.
[9] Zuscik MJ, Hilton MJ, Zhang XP, Chen D, O’Keefe RJ. Regulation of chondrogenesis and chondrocyte differentiation by stress. J Clin Invest , 2008, 118(2): 429-438.
[10] 谷志远, 胡莹, 张银凯, 冯剑颖, 胡济安. 髁突软骨的细胞分层及其功能研究. 中华口腔医学杂志, 2004, 39(5): 366.
[11] Schmid TM, Linsenmayer TF. Immunohistochemical localization of short chain cartilage collagen (type X) in avian tissues. J Cell Biol , 1985, 100(2): 598-605.
[12] Ornitz DM, Marie PJ. FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. Genes Dev , 2002, 16(12): 1446-1465.
[13] Yasuda T, Nah HD, Laurita J, Kinumatsu T, Shibukawa Y, Shibutani T, Minugh-Purvis N, Pacifici M, Koyama E. Muenke syndrome mutation, fgfr3 P244R , causes TMJ defects. J Dent Res , 2012, 91(7): 683-689.
[14] Lin Y, Ai SM, Chen C, Liu XL, Luo LX, Ye SB, Liang XW, Zhu Y, Yang HS, Liu YZ. Ala344Pro mutation in the Fgfr 2 gene and related clinical findings in one Chinese family with Crouzon syndrome. Mol Vis , 2012, 18: 1278-1282.
[15] Lajeunie E, Ma HW, Bonaventure J, Munnich A, Le Merrer M, Renier D. FGFR2 mutations in Pfeiffer syndrome. Nat Genet , 1995, 9(2): 108.

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

FGFR2功能增强对小鼠下颌骨髁突发育影响

A gain-of-function mutation in FGFR2 influences mandibular condylar development on mice

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 1

编辑推荐

Metrics