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Effect of CD4+Foxp3+ regulatory T cell on the osteogenic differentiation of bone marrow mesenchymal stem cells |
LIU Cuicui WU Yaxing ZHANG Shuting LI Xiangxin ZHANG Jing▲ |
Affiliated Xuzhou Clinical College, Xuzhou Medical University, Jiangsu Province, Xuzhou 221000, China
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Abstract Objective To investigate the effect of CD4+Foxp3+ regulatory T cell on the osteogenic differentiation of bone marrow mesenchymal stem cell (BMMSC). Methods The experiment was divided into three groups, the control group consisted of CD4+ T cells and BMMSC; the experimental group consisted of regulatory T cells and BMMSC; the inhibitory group consisted of regulatory T cells and BMMSC and added GW4869 (exosome inhibitor). Mineralization induction was performed in all three groups. ALP expression and activity were detected by alkaline phosphatase (ALP) staining and activity at day 0 and 7, mineralization nodules formation and calcium content were detected by alizarin red staining and calcium content analysis at day 0 and 21, levels of bone differentiation genes ALP, OCN, and Runx2 mRNA were detected by PCR at day 7. Results the ALP staining area and ALP activity in the experimental group were higher than those in the control group (P<0.01). The formation and calcium content of mineralized nodules stained with alizarin red were higher than those in the control group (P<0.01), and the expression levels of ALP, OCN, and Runx2 mRNA were higher than those in the control group (P<0.01). The ALP staining area and ALP activity in the inhibitory group were lower than those in the experimental group (P<0.01), the formation and calcium content of mineralized nodules stained with alizarin red were lower than those in the experimental group (P<0.01), and the expression levels of ALP, OCN, and Runx2 mRNA were lower than those in the experimental group (P<0.01). Conclusion Tregs could promote the osteogenic differentiation of BMMSC, and Tregs exosomes may participate in this process.
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[1] Ouchi T,Nakagawa T. Mesenchymal stem cell-based tissue regeneration therapies for periodontitis [J]. Regen Ther,2020, 14:72-78.
[2] Zhao Q,Li G,Wang T,et al. Human Periodontal Ligament Stem Cells Transplanted with Nanohydroxyapatite/Chitosan/ Gelatin 3D Porous Scaffolds Promote Jaw Bone Regeneration in Swine [J]. Stem Cells Dev,2021,30(10):548-559.
[3] Shang L,Shao J,Ge S. Immunomodulatory functions of oral mesenchymal stem cells:Novel force for tissue regeneration and disease therapy [J]. J Leukoc Biol,2021,110(3):539- 552.
[4] Perez JR,Kouroupis D,Li DJ,et al. Tissue engineering and cell-based therapies for fractures and bone defects [J]. Front Bioeng Biotechnol,2018,6:105.
[5] Chen FM,Gao LN,Tian BM,et al. Treatment of periodontal intrabony defects using autologous periodontal ligament stem cells: a randomized clinical trial [J]. Stem Cell Res Ther,2016,7:33.
[6] Fakhry M,Hamade E,Badran B,et al. Molecular mechanisms of mesenchymal stem cell differentiation towards osteoblasts [J]. World J Stem Cells,2013,5:48-136.
[7] Selck C,Dominguez-Villar M. Antigen-Specific Regulatory T Cell Therapy in Autoimmune Diseases and Transplantation [J]. Front Immunol,2021,12:661875.
[8] Chen Y,Colello J,Jarjour W,et al. Cellular Metabolic Regulation in the Differentiation and Function of Regulatory T Cells [J]. Cells,2019,8(2):188.
[9] Gaffen SL,Moutsopoulos NM. Regulation of host-microbe interactions at oral mucosal barriers by type 17 immunity [J]. Sci Immunol,2020,5(43).
[10] Shao Y,Pan X,Fu R. Role and Function of T Cell-Derived Exosomes and Their Therapeutic Value [J]. Mediators Inflamm,2021,2021:8481013.
[11] 李晨晨,吴亚星,刘翠翠,等.炎症微环境下骨髓间充质干细胞上清液内细胞因子表达及其对成骨分化的影响[J].蚌埠医学院学报,2022,47(6):635-639.
[12] Xu J,Fu L,Bai J,et al. Low-dose IL-34 has no effect on osteoclastogenesis but promotes osteogenesis of hBMSCs partly via activation of the PI3K/AKT and ERK signaling pathways [J]. Stem Cell Res Ther,2021,12(1):268.
[13] Qiu R,Zhou L,Ma Y,et al. Regulatory T Cell Plasticity and Stability and Autoimmune Diseases [J]. Clin Rev Allergy Immunol,2020,58(1):52-70.
[14] G?觟schl L,Scheinecker C,Bonelli M. Treg cells in autoimmunity: from identification to Treg-based therapies [J]. Semin Immunopathol,2019,41(3):301-314.
[15] Salek Farrokhi A,Zarnani AH,Rezaei Kahmini F,et al. Mesenchymal stem cells induce expansion of regulatory T cells in abortion-prone mice [J]. Reproduction,2021,161(4):477-487.
[16] Shao BY,Wang L,Yu Y,et al. Effects of CD4+ T lymphocytes from ovariectomized mice on bone marrow mesenchymal stem cell proliferation and osteogenic differentiation [J]. Exp Ther Med,2020,20(5):84.
[17] Abe Y,Ochiai D,Taguchi M,et al. Human Amniotic Fluid Stem Cells Ameliorate Thioglycollate-Induced Peritonitis by Increasing Tregs in Mice [J]. Int J Mol Sci,2022,23(12): 6433.
[18] Caplan HW,Prabhakara KS,Toledano Furman NE,et al. Combination therapy with Treg and mesenchymal stromal cells enhances potency and attenuation of inflammation after traumatic brain injury compared to monotherapy [J]. Stem Cells,2021,39(3):358-370.
[19] Xu F,Guanghao C,Liang Y,et al. Treg-promoted New Bone Formation Through Suppressing TH17 by Secreting Interleukin-10 in Ankylosing Spondylitis [J]. Spine,2019,44(23):E1349-E1355.
[20] Negi N,Griffin MD. Effects of mesenchymal stromal cells on regulatory T cells: Current understanding and clinical relevance [J]. Stem Cells,2020,38(5):596-605.
[21] Zhou Y,Zhang Y,Gong H,et al. The Role of Exosomes and Their Applications in Cancer [J]. Int J Mol Sci,2021,22(22):12204.
[22] Tung SL,Fanelli G,Matthews RI,et al. Regulatory T Cell Extracellular Vesicles Modify T-Effector Cell Cytokine Production and Protect Against Human Skin Allograft Damage [J]. Front Cell Dev Biol,2020,8:317.
[23] Yang C,Yuan F,Shao W,et al. Protective role of exosomes derived from regulatory T cells against inflammation and apoptosis of BV-2 microglia under oxygen-glucose deprivation/reperfusion challenge [J]. Genet Mol Biol,2022,19, 45(4):e20220119.
[24] Xiong W,Li C,Kong G,et al. Treg cell-derived exosomes miR-709 attenuates microglia pyroptosis and promotes motor function recovery after spinal cord injury [J]. J Nanobiotechnology,2022,20(1):529.
[25] Shin S,Jung I,Jung D,et al. Novel antitumor therapeutic strategy using CD4+ T cell-derived extracellular vesicles. Biomaterials [J]. 2022,289:121765. |
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