Fgf9在小鼠下颌骨发育软骨成骨及膜内成骨过程中的作用探讨

doi:10.19438/j.cjoms.2021.04.004

中国口腔颌面外科杂志 ›› 2021, Vol. 19 ›› Issue (4): 309-314.doi: 10.19438/j.cjoms.2021.04.004

Fgf9在小鼠下颌骨发育软骨成骨及膜内成骨过程中的作用探讨

李若梅, 翁梦佳, 孙一丹, 陈振琦

上海交通大学医学院附属第九人民医院口腔正畸科,上海交通大学口腔医学院,国家口腔医学中心, 国家口腔疾病临床医学研究中心,上海市口腔医学重点实验室,上海 200011

收稿日期:2020-12-21 修回日期:2021-03-17 出版日期:2021-07-20 发布日期:2021-08-05
通讯作者: 陈振琦,E-mail：orthochen@yeah.net
作者简介:李若梅（1994-）,女,在读硕士研究生,E-mail：cindypbelf@foxmail.com

Fgf9 regulated murine mandibular development by promoting endochondral and intramembranous ossification

LI Ruo-mei, WENG Meng-jia, SUN Yi-dan, CHEN Zhen-qi

Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology. Shanghai 200011, China

Received:2020-12-21 Revised:2021-03-17 Online:2021-07-20 Published:2021-08-05

摘要/Abstract

摘要： 目的： 观察成纤维细胞生长因子9（fibroblast growth factor 9, Fgf9）基因敲除小鼠模型中下颌骨发育的骨质变化,探讨Fgf9参与下颌骨发育中的软骨成骨和膜内成骨的过程。方法： 建立Fgf9基因敲除小鼠模型（Fgf9^-/-）。利用显微CT技术检测Fgf9^-/-的下颌骨形态及骨参数,利用原位杂交对Fgf9在下颌骨的表达进行定位,应用H-E染色和番红固绿染色对胚胎的髁突、麦克尔软骨、膜内成骨区进行组织学分析。采用 SPSS 25.0软件包对数据进行统计学处理。结果： 显微CT显示,Fgf9^-/-髁突、喙突、下颌角区形态不佳,Tb.N降低、Tb.Sp增高、BMD下降。原位杂交显示,Fgf9广泛表达于软骨膜、软骨细胞、成骨细胞、血管内皮细胞及软骨及骨的周围间充质细胞。H-E染色与番红固绿染色显示, Fgf9^-/-髁突软骨形态畸形、软骨基质分泌不足、肥大软骨细胞比例下降、周围骨小梁纤细且分散。Fgf9^-/-麦克尔软骨前段软骨成骨及下颌骨体部的膜内成骨形成的骨小梁纤细、分散且矿化不良。结论： Fgf9在髁突软骨成骨过程中,促进软骨细胞分化成熟、分泌软骨基质,同时可能促进成骨细胞分泌骨基质,从而形成粗壮且健康的骨小梁。Fgf9参与膜内成骨,通过调控成骨细胞,促进骨小梁形成和矿化。

关键词: 成纤维细胞生长因子9, 下颌骨发育, 软骨成骨, 膜内成骨

Abstract: PURPOSE: To investigate the role of fibroblast growth factor 9 (Fgf9) in endochondral and intramembranous ossification during mandibular development by analyzing the mandibular phenotype of Fgf9 knockout mice. METHODS: A Fgf9 gene-knock-out mice model was established for understanding the role of Fgf9 during mandibular development. Micro-CT was applied for analyzing the bone morphology and parameters. In situ hybridization was used for detecting the expression pattern of Fgf9 in mandible. H-E and Safranin O-fast green staining were used for histologic analysis of condyle, Meckel's cartilage, and the region generated by intramembranous ossification. SPSS 25.0 software was performed for statistical analysis. RESULTS: Micro-CT showed defective condyle, coracoid process, and mandibular angle in Fgf9^-/-mice with Tb. N and BMD decreased, and Tb. Sp increased. In situ hybridization indicated that Fgf9 was widely expressed in perichondrium, chondrocyte, osteoblast, endothelial cells, and mesenchyme around the cartilage and trabecular bone. H-E and Safranin O-fast green staining exhibited a malformed condyle cartilage with an inadequate secretion of cartilage matrix, decreased proportion of hypertrophic chondrocyte, and defective and dispersive trabecular bone. Moreover, the trabecular bone in the regions of the anterior part of the Meckel's cartilage and the intramembranous ossification was defective, dispersive, and hypo-mineralized. CONCLUSIONS: During mandibular development, Fgf9 participates in the endochondral ossification of the condyle by promoting maturation and secretion of the chondrocyte. Meanwhile, it is able to facilitate the secretion of osteoblast for pursuit of well-morphed trabecular bone. Furthermore, Fgf9 is involved in intramembranous ossification by regulating the osteoblast during the formation and mineralization of the trabecular bone.

Key words: Fibroblast growth factor 9, Mandibular development, Endochondral ossification, Intramembranous ossification

中图分类号:

R783.5

李若梅, 翁梦佳, 孙一丹, 陈振琦. Fgf9在小鼠下颌骨发育软骨成骨及膜内成骨过程中的作用探讨[J]. 中国口腔颌面外科杂志, 2021, 19(4): 309-314.

LI Ruo-mei, WENG Meng-jia, SUN Yi-dan, CHEN Zhen-qi. Fgf9 regulated murine mandibular development by promoting endochondral and intramembranous ossification[J]. China J Oral Maxillofac Surg, 2021, 19(4): 309-314.

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Fgf9在小鼠下颌骨发育软骨成骨及膜内成骨过程中的作用探讨

Fgf9 regulated murine mandibular development by promoting endochondral and intramembranous ossification

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