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

• 研究报告 • 上一篇    下一篇

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. 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. 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: 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