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Downregulated FGFR3 Expression Inhibits In Vitro Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells of Mice with TBXT Gene Mutation

  • Translated from Kletochnye Tekhnologii v Biologii i Meditsine (Cell Technologies in Biology and Medicine)
  • Published:
Bulletin of Experimental Biology and Medicine Aims and scope

We studied the effect of fibroblast growth factor receptor 3 (FGFR3) inhibitor BGJ-398 on the differentiation of bone marrow mesenchymal stem cells (BM MSC) into osteoblasts in wild type (wt) mice and in animals with mutation in TBXT gene (mt) and possible differences in the pluripotency of these cells. Cytology tests showed that the cultured BM MSC could differentiate into osteoblasts and adipocytes. The effect of different BGJ-398 concentrations on the expression of FGFR3, RUNX2, SMAD1, SMAD4, SMAD5, SMAD6, SMAD7, and SMAD8 were studied by quantitative reverse transcription PCR. The expression of RUNX2 protein was evaluated by Western blotting. BM MSC of mt and wt mice did not differ in pluripotency and expressed the same membrane marker antigens. BGJ-398 inhibitor reduced the expression of FGFR3 and RUNX2. In BM MSC from mt and wt mice have similar gene expression (and its changing) in FGFR3, RUNX2, SMAD1, SMAD4, SMAD5, SMAD6, SMAD7, and SMAD8 genes. Thus, our experiments confirmed the effect of decreased expression of FGFR3 on osteogenic differentiation of BM MSC from wt and mt mice. However, BM MSC from mt and wt mice did not differ in pluripotency and are an adequate model for laboratory research.

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References

  1. Dobrovolskaïa-Zavadskaïa N. Sur la mortification spontanée de la queue chez la Souris nouveau-née et sur l’existence d’un caractère (facteur) héréditaire “non viable”. C R Seances Soc. Biol. Fil. 1927;97:114-116.

    Google Scholar 

  2. Kavka AI, Green JB. Tales of tails: Brachyury and the T-box genes. Biochim. Biophys. Acta. 1997;1333(2):F73-F84. https://doi.org/10.1016/s0304-419x(97)00016-4

    Article  CAS  PubMed  Google Scholar 

  3. Herrmann BG. Action of the Brachyury gene in mouse embryogenesis. Ciba Found Symp. 1992;165:78-86; discussion 86-91. https://doi.org/10.1002/9780470514221.ch5

  4. Zhi D, Da L, Liu M, Cheng C, Zhang Y, Wang X, Li X, Tian Z, Yang Y, He T, Long X, Wei W, Cao G. Whole Genome Sequencing of Hulunbuir Short-Tailed Sheep for Identifying Candidate Genes Related to the Short-Tail Phenotype. G3 (Bethesda). 2018;8(2):377-383. https://doi.org/10.1534/g3.117.300307

  5. Pennimpede T, Proske J, König A, Vidigal JA, Morkel M, Bramsen JB, Herrmann BG, Wittler L. In vivo knockdown of Brachyury results in skeletal defects and urorectal malformations resembling caudal regression syndrome. Dev. Biol. 2012;372(1):55-67. https://doi.org/10.1016/j.ydbio.2012.09.003

    Article  CAS  PubMed  Google Scholar 

  6. Kispert A, Herrmann BG. Immunohistochemical analysis of the Brachyury protein in wild-type and mutant mouse embryos. Dev. Biol. 1994;161(1):179-193. https://doi.org/10.1006/dbio.1994.1019

    Article  PubMed  Google Scholar 

  7. Marie PJ, Miraoui H, Sévère N. FGF/FGFR signaling in bone formation: progress and perspectives. Growth Factors. 2012;30(2):117-123. https://doi.org/10.3109/08977194.2012.656761

    Article  CAS  PubMed  Google Scholar 

  8. Ding DC, Shyu WC, Lin SZ. Mesenchymal stem cells. Cell. Transplant. 2011;20(1):5-14. https://doi.org/10.3727/096368910X

    Article  PubMed  Google Scholar 

  9. Dailey L, Ambrosetti D, Mansukhani A, Basilico C. Mechanisms underlying differential responses to FGF signaling. Cytokine Growth Factor Rev. 2005;16(2):233-247. https://doi.org/10.1016/j.cytogfr.2005.01.007

    Article  CAS  PubMed  Google Scholar 

  10. Komori T. Regulation of Proliferation, Differentiation and Functions of Osteoblasts by Runx2. Int. J. Mol. Sci. 2019;20(7):1694. https://doi.org/10.3390/ijms20071694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Valverde-Franco G, Liu H, Davidson D, Chai S, Valderrama-Carvajal H, Goltzman D, Ornitz DM, Henderson JE. Defective bone mineralization and osteopenia in young adult FGFR3-/- mice. Hum. Mol. Genet. 2004;13(3):271-284. https://doi.org/10.1093/hmg/ddh034

    Article  CAS  PubMed  Google Scholar 

  12. Su N, Sun Q, Li C, Lu X, Qi H, Chen S, Yang J, Du X, Zhao L, He Q, Jin M, Shen Y, Chen D, Chen L. Gain-of-function mutation in FGFR3 in mice leads to decreased bone mass by affecting both osteoblastogenesis and osteoclastogenesis. Hum. Mol. Genet. 2010;19(7):1199-1210. https://doi.org/10.1093/hmg/ddp590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Matsushita T, Wilcox WR, Chan YY, Kawanami A, Bükülmez H, Balmes G, Krejci P, Mekikian PB, Otani K, Yamaura I, Warman ML, Givol D, Murakami S. FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway. Hum. Mol. Genet. 2009;18(2):227-240. https://doi.org/10.1093/hmg/ddn339

    Article  CAS  PubMed  Google Scholar 

  14. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143-147. https://doi.org/10.1126/science.284.5411.143

    Article  CAS  PubMed  Google Scholar 

  15. Julien A, Perrin S, Duchamp de Lageneste O, Carvalho C, Bensidhoum M, Legeai-Mallet L, Colnot C. FGFR3 in Periosteal Cells Drives Cartilage-to-Bone Transformation in Bone Repair. Stem Cell Reports. 2020;15(4):955-967. https://doi.org/10.1016/j.stemcr.2020.08.005

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Correspondence to G. F. Cao.

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Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 4, pp. 269-279, December, 2022

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Su, H., Yang, G., Yang, H.X. et al. Downregulated FGFR3 Expression Inhibits In Vitro Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells of Mice with TBXT Gene Mutation. Bull Exp Biol Med 174, 578–584 (2023). https://doi.org/10.1007/s10517-023-05750-0

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