成纤维细胞生长因子受体在成骨细胞中的表达及作用研究

莫奇非; 杨鹏; 苏楠; 陈林

doi:10.16016/j.1000-5404.201907008

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成纤维细胞生长因子受体在成骨细胞中的表达及作用研究

基础医学 | 更新时间：2026-01-09

- 成纤维细胞生长因子受体在成骨细胞中的表达及作用研究
- Expression of fibroblast growth factor receptor and its role in regulating osteoblast differentiation
- 第三军医大学学报 2019年41卷第24期页码：2386-2392
- 作者机构：
  
  400042 重庆，陆军军医大学(第三军医大学)野战外科研究所:骨质疏松分骨发育中心，战伤组织修复与康复医学研究室，全军军事训练伤仿治与康复室，创伤、烧伤与复合伤国家重点试验室
- 作者简介：
  
  [ 陈林，E-mail:linchen70@163.com CHEN Lin, E-mail: linchen70@163.com
- 基金信息：
  
  国家自然科学基金面上项目(81870621);国家重点研发计划(2018YFA0800802)
- DOI：10.16016/j.1000-5404.201907008
  中图分类号： R322.71;R329-33;R329.2
- 收稿：2019-07-02，
  
  修回：2019-08-16，
  
  纸质出版：2019-12-30
- 稿件说明：
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莫奇非, 杨鹏, 苏楠, 等. 成纤维细胞生长因子受体在成骨细胞中的表达及作用研究[J]. 第三军医大学学报, 2019,41(24):2386-2392.

Qifei MO, Peng YANG, Nan SU, et al. Expression of fibroblast growth factor receptor and its role in regulating osteoblast differentiation[J]. Journal of Third Military Medical University, 2019, 41(24): 2386-2392.
莫奇非, 杨鹏, 苏楠, 等. 成纤维细胞生长因子受体在成骨细胞中的表达及作用研究[J]. 第三军医大学学报, 2019,41(24):2386-2392. DOI： 10.16016/j.1000-5404.201907008.

Qifei MO, Peng YANG, Nan SU, et al. Expression of fibroblast growth factor receptor and its role in regulating osteoblast differentiation[J]. Journal of Third Military Medical University, 2019, 41(24): 2386-2392. DOI： 10.16016/j.1000-5404.201907008.

摘要

目的

检测成纤维细胞生长因子受体(fibroblast growth factor receptors，FGFRs)1-3在成骨分化不同阶段的表达变化，并明确FGFR信号在成骨分化中的重要作用。

方法

利用原代成骨细胞和成骨细胞系MC3T3-E1进行成骨诱导，通过形态观察、碱性磷酸酶(alkaline phosphatase，ALP)染色和茜素红染色鉴定细胞分化情况，qRT-PCR和Western blot检测成骨分化相关基因和FGFR1-3的表达，并通过阻断FGFR信号观察成骨细胞分化的变化。

结果

原代成骨细胞ALP染色和茜素红染色阳性，成骨分化相关基因COL 1α、RUNX2、OPN表达增加，在成骨细胞系MC3T3-E1实验中得到了类似结果，而且FGFR1、FGFR2和FGFR3在成骨分化过程中表达增加，阻断FGFR信号可以显著抑制成骨分化，提示FGFR信号参与了成骨细胞分化调控。

结论

FGFR信号促进成骨细胞成骨分化。

Abstract

Objective

To investigate the changes in the expression of fibroblast growth factor receptors 1-3 (FGFR1-3) at different stages of osteogenic differentiation and clarify the role of FGFR signaling in osteogenic differentiation.

Methods

Mouse osteoblasts in primary culture and osteoblast cell line MC3T3-E1 were induced for osteogenic differentiation

and the cell differentiation was identified by morphological observation

alkaline phosphatase (ALP) staining and alizarin red staining. qRT-PCR and Western blotting were used to detect the expression of FGFR1-3 and the genes involved in osteogenic differentiation

and the effect of blocking FGFR signaling on osteoblast differentiation was observed.

Results

The primary mouse osteoblasts were positive to ALP staining and alizarin red staining. The expression of COL 1α

RUNX2 and OPN was increased during osteogenic differentiation in both mouse osteoblasts and MC3T3-E1 cells. The expression of FGFR1

FGFR2 and FGFR3 was also increased in the cells during osteogenic differentiation

and blocking FGFR signaling significantly inhibited osteogenic differentiation of the cells

suggesting the regulatory role of FGFR signaling in osteoblast differentiation.

Conclusion

FGFR signaling promotes osteogenic differentiation of osteoblasts.

关键词

Keywords

references

DIRCKX N, MOORER M C, CLEMENS T L, et al . The role of osteoblasts in energy homeostasis[J ] . Nat Rev Endocrinol, 2019, 15(11): 651-665. DOI: 10.1038/s41574-019-0246-y.

ILAS D C, CHURCHMAN S M, BABOOLAL T, et al . The simultaneous analysis of mesenchymal stem cells and early osteocytes accumulation in osteoarthritic femoral head sclerotic bone[J ] . Rheumatology (Oxford), 2019, 58(10): 1777-1783. DOI: 10.1093/rheumatology/kez130.

BRYLKA L J, SCHINKE T. Chemokines in physiological and pathological bone remodeling[J]. Front Immunol, 2019, 10: 2182. DOI: 10.3389/fimmu.2019.02182.

SARGAR K M, SINGH A K, KAO S C. Imaging of skeletal disorders caused by fibroblast growth factor receptor gene mutations[J]. Radio Graphics, 2017, 37(6): 1813-1830. DOI: 10.1148/rg.2017170017.

ORNITZ D M, MARIE P J. Fibroblast growth factor signaling in skeletal development and disease[J]. Genes Dev, 2015, 29(14): 1463-1486. DOI: 10.1101/gad.266551.115.

MAK W, SHAO X Y, DUNSTAN C R, et al . Biphasic glucocorticoid-dependent regulation of Wnt expression and its inhibitors in mature osteoblastic cells[J ] . Calcif Tissue Int, 2009, 85(6): 538-545. DOI: 10.1007/s00223-009-9303-1.

ZHOU H, MAK W, ZHENG Y, et al . Osteoblasts directly control lineage commitment of mesenchymal progenitor cells through Wnt signaling[J ] . J Biol Chem, 2008, 283(4): 1936-1945. DOI: 10.1074/jbc.M702687200.

TIONG K H, MAH L Y, LEONG C. Functional roles of fibroblast growth factor receptors (FGFRs) signaling in human cancers[J]. Apoptosis, 2013, 18(12): 1447-1468. DOI: 10.1007/s10495-013-0886-7.

LI D, YUAN Q, YU K, et al . Mg-Zn-Mn alloy extract induces the angiogenesis of human umbilical vein endothelial cells via FGF/FGFR signaling pathway[J ] . Biochem Biophys Res Commun, 2019, 514(3): 618-624. DOI: 10.1016/j.bbrc.2019.04.198.

KANG J, CHOI Y J, SEO B Y, et al . A Selective FGFR inhibitor AZD4547 suppresses RANKL/M-CSF/OPG-dependent ostoclastogenesis and breast cancer growth in the metastatic bone microenvironment[J ] . Sci Rep, 2019, 9(1): 8726. DOI: 10.1038/s41598-019-45278-w.

[BENGUR F B, EKMEKCI C G, KARAARSLAN E, et al . P.Ser348Cys mutation in FGFR3 gene leads to "Mild ACH /Severe HCH" phenotype[J ] . Eur J Med Genet, 2019 DOI: 10.1016/j.ejmg.2019.04.016 http://dx.doi.org/10.1016/j.ejmg.2019.04.016 ..

CHANG I J, SUN A, BOUCHARD M L, et al . Novel phenotype of achondroplasia due to biallelic FGFR3 pathogenic variants[J ] . Am J Med Genet A, 2018, 176(7): 1675-1679. DOI: 10.1002/ajmg.a.38839.

KUNOVA BOSAKOVA M, VARECHA M, HAMPL M, et al . Regulation of ciliary function by fibroblast growth factor signaling identifies FGFR3-related disorders achondroplasia and thanatophoric dysplasia as ciliopathies[J ] . Hum Mol Genet, 2018, 27(6): 1093-1105. DOI: 10.1093/hmg/ddy031.

COLL G, ABED RABBO F, JECKO V, et al . The growth of the posterior cranial Fossa in FGFR2-induced faciocraniosynostosis: A review[J ] . Neurochirurgie, 2019: 65(5): 221-227. DOI: 10.1016/j.neuchi.2019.09.005.

MOTCH PERRINE S M, WU M, STEPHENS N B, et al . Mandibular dysmorphology due to abnormal embryonic osteogenesis in FGFR2-related craniosynostosis mice[J ] . Dis Model Mech, 2019, 12(5): dmm038513. DOI: 10.1242/dmm.038513.

KÄHKÖNEN T E, IVASKA K K, JIANG M, et al . Role of fibroblast growth factor receptors (FGFR) and FGFR like-1 (FGFRL1) in mesenchymal stromal cell differentiation to osteoblasts and adipocytes[J ] . Mol Cell Endocrinol, 2018, 461: 194-204. DOI: 10.1016/j.mce.2017.09.015.

ZHANG W, XUE D T, HU D C, et al . Secreted klotho protein attenuates osteogenic differentiation of human bone marrow mesenchymal stem cells in vitro via inactivation of the FGFR1/ERK signaling pathway[J ] . Growth Factors, 2015, 33(5/6): 356-365. DOI: 10.3109/08977194.2015.1108313..

SIMANN M, LE BLANC S, SCHNEIDER V, et al . Canonical FGFs prevent osteogenic lineage commitment and differentiation of human bone marrow stromal cells via ERK1/2 signaling[J ] . J Cell Biochem, 2017, 118(2): 263-275. DOI: 10.1002/jcb.25631.

KOMORI T. Regulation of proliferation, differentiation and functions of osteoblasts by Runx2[J]. Int J Mol Sci, 2019, 20(7): 1694. DOI: 10.3390/ijms20071694.

CHEN H G, SUN X D, YIN L J, et al . PTH 1-34 ameliorates the osteopenia and delayed healing of stabilized tibia fracture in mice with achondroplasia resulting from gain-of-function mutation of FGFR3[J ] . Int J Biol Sci, 2017, 13(10): 1254-1265. DOI: 10.7150/ijbs.21258.

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