Foxl2基因对小鼠软骨及骨发育的调控研究

摘要
图/表
参考文献
相关文章 (0)

全文: PDF (3357 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要目的 Foxl2转录因子单倍剂量不足会导致小睑裂综合征(blepharophimosis ptosis epicanthus inversus syndrome，BPES)，表现为眼睑异常和卵巢功能早衰。小鼠Foxl2基因缺乏亦导致眼睑、额头缺陷和雌性性腺发育不全。本试验旨在研究Foxl2缺乏对小鼠出生后的生长和胚胎期骨、软骨形成的影响。方法对比雄性Foxl2^－/－与野生型小鼠在不同发育阶段的特征，测量绘制生长曲线。骨骼用阿尔新兰/茜素红、硝酸银染色，行免疫荧光分析和共聚焦显微镜下分析。RT-qPCR分析生长激素(growth hormone，GH)/胰岛素样生长因子1(insulin like grouth factor-1，IGF1)通路以评估下丘脑-垂体-骨轴上标记物的表达。结果较之野生型小鼠，Foxl2敲除小鼠表现出较小体型、骨骼异常、软骨和骨矿化缺陷、GH/IGF1轴下调。结论 Foxl2是生长发育、软骨和骨形成的过程的主要转录因子。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	薛建利

关键词 ： Foxl2, 骨发育, 软骨发育, 小鼠

Abstract：Objective Haploinsufficiency of the Foxl2 transcription factor in humans causes Blepharophimosis/Ptosis/Epicanthus Inversus syndrome(BPES)，characterized by eyelid anomalies and premature ovarian failure.Mice lacking Foxl2 recapitulate human eyelid/forehead defects and undergo female gonadal dysgenesis.Our experiment aims to explore the influence of lacking Foxl2 in postnatal growth and embryonic bone and cartilage formation in mice.Methods Foxl2^－/－ male mice at different stages of development have been characterized and compared to wild type.Body length and weight were measured and growth curves were created.Skeletons were stained with alcian blue and/or alizarin red.Bone and cartilage formation was analyzed by Von Kossa staining and immunofluorescence using anti-Foxl2 antibodies followed by confocal microscopy.Analysis of the GH-IGF1 pathway was done evaluating the expression of several hypothalamic-pituitary-bone axis markers by RT-qPCR.Results Compared to wild-type，Foxl2 null mice are smaller and show skeletal abnormalities and defects in cartilage and bone mineralization，with down-regulation of the GH/IGF1 axis.Conclusion Our results support Foxl2 as a master transcription factor in a spectrum of developmental processes，including growth，cartilage and bone formation.

Key words： foxl2 bone development cartilage development mice

基金资助:陕西省社会发展科技攻关项目(2016SF-187)

作者简介: 薛建利(1981－ )，男，主治医师，西安交通大学第二附属医院骨三科，710004

引用本文:

薛建利. Foxl2基因对小鼠软骨及骨发育的调控研究[J]. 实用骨科杂志, 2017, 23(2): 142-146.
Xue Jianli. Modulations of FOXL2 on Cartilage and Skeletal Development in Mice. sygkzz, 2017, 23(2): 142-146.

链接本文:

http://www.sygkzz.com/CN/ 或 http://www.sygkzz.com/CN/Y2017/V23/I2/142

［1］Caburet S，Georges A，L’H-te D，et al.The transcription factor FOXL2：at the crossroads of ovarian physiology and pathology［J］.Mol Cell Endocrinol，2012，356(1-2)：55-64.
［2］Verdin H，De Baere E.FOXL2 impairment in human disease［J］.Horm Res Paediatr，2012，77(1)：2-11.
［3］Georges A，Auguste A，Bessière L，et al.FOXL2：a central transcription factor of the ovary［J］.J Mol Endocrinol，2014，52(1)：17-33.
［4］Uda M，Ottolenghi C，Crisponi L，et al.Foxl2 disruption causes mouse ovarian failure by pervasive blockage of follicle development［J］.Hum Mol Genet，2004，13(11)：1171-1181.
［5］Garcia-Ortiz JE，Pelosi E，Omari S，et al.Foxl2 functions in sex determination and histogenesis throughout mouse ovary development［J］.BMC Dev Biol，2009，9(1)：36.
［6］Shi F，Ding S，Zhao S，et al.A piggyBac insertion disrupts Foxl2 expression that mimics BPES syndrome in mice［J］.Hum Mol Genet，2014，23(14)：3792-3800.
［7］Ellsworth BS，Egashira N，Haller JL，et al.FOXL2 in the pituitary：molecular，genetic，and developmental analysis［J］.Mol Endocrinol，2006，20(11)：2796-2805.
［8］Egashira N，Takekoshi S，Takei M，et al.Expression of FOXL2 in human normal pituitaries and pituitary adenomas［J］.Mod Pathol，2011，24(6)：765-773.
［9］Tran S，Zhou X，Lafleur C，et al.Impaired fertility and FSH synthesis in gonadotrope-specific Foxl2 knockout mice［J］.Mol Endocrinol，2013，27(3)：407-421.
［10］Burdan F，Szumito，Dudka J，et al.Morphological studies in modern teratological investigations［J］.Folia Morphol(Warsz)，2005，64(1)：1-8.
［11］唐新，郑果，黄强，等.人骨关节炎软骨细胞的体外培养及细胞形态学分析［J］.实用骨科杂志，2015，21(7)：614-618.
［12］Versteyhe S，Klaproth B，Borup R，et al.IGF-I，IGF-Ⅱ，and Insulin Stimulate Different Gene Expression Responses through Binding to the IGF-I Receptor［J］.Front Endocrinol(Lausanne)，2013，4(98)：98.
［13］Tahimic CG，Wang Y，Bikle DD.Anabolic effects of IGF-1 signaling on the skeleton［J］.Front Endocrinol(Lausanne)，2013(4)：6.
［14］吴耀国，迟志永.成骨细胞局部调节的信号传导通路［J］.实用骨科杂志，2014，20(7)：628-632.
［15］Sauka-Spengler T，Bronner-Fraser M.A gene regulatory network orchestrates neural crest formation［J］.Nat Rev Mol Cell Biol，2008，9(7)：557-568.