IL-18-Mediated SLC7A5 Overexpression Enhances Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells via the c-MYC Pathway.
IL-18-Mediated SLC7A5 Overexpression Enhances Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells via the c-MYC Pathway.
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DOI：
10.3389/fcell.2021.748831
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发表时间：
2021
影响因子：
5.5
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Ni F;Zhang T;Xiao W;Dong H;Gao J;Liu Y;Li J
目的：探讨IL-18对人骨髓间充质干细胞（hBMSCs）成骨分化的调控作用。 研究方法：为了评估IL-18是否通过c-MYC/SLC 7A 5轴影响hBMSCs的成骨分化，进行IL-18剂量-反应和时间过程实验以评估其对成骨分化的影响。为了证实成骨分化，进行茜素红染色钙测量。使用RT-qPCR和蛋白质印迹法测定骨特异性标志物ALP、RUNX 2和BMP 2以及SLC 7A 5和c-MYC的表达水平。此外，通过免疫荧光评价SLC 7A 5和c-MYC表达。为了阐明SLC 7A 5和c-MYC在成骨细胞分化中的作用，用SLC 7A 5或c-MYC siRNA转染细胞，或用SLC 7A 5特异性抑制剂JPH 203和c-MYC特异性抑制剂10058-F4处理细胞，并评估SLC 7A 5、c-MYC和骨特异性标志物ALP、RUNX 2和BMP 2的表达。 结果如下：我们的结果表明，IL-18增加了hBMSCs中的钙沉积，并上调了SLC 7A 5、c-MYC、ALP、RUNX 2和BMP 2的表达。使用SiRNA沉默SLC 7A 5或c-MYC减少了ALP、RUNX 2和BMP 2的表达，而IL-18处理部分逆转了SiRNA的抑制作用。通过用SLC 7A 5和c-MYC特异性抑制剂处理hBMSC获得类似的结果，导致IL-18对hBMSC的成骨作用显著降低。 结论：总之，我们的研究结果表明，IL-18通过SLC 7A 5/c-MYC途径促进hBMSCs的成骨分化，因此，可能在骨折愈合中发挥重要作用。这些发现将为脾切除术后骨折延迟愈合提供新的治疗策略。
Objective: To investigate the role of IL-18 in the regulation of osteogenic differentiation in human bone marrow mesenchymal stem cells (hBMSCs). Methods: To assess whether IL-18 affects the osteogenic differentiation of hBMSCs through the c-MYC/SLC7A5 axis, IL-18 dose-response and time-course experiments were performed to evaluate its impact on osteogenic differentiation. To confirm osteogenic differentiation, alizarin red staining calcium measurement were performed. RT-qPCR and western blotting were used to determine the expression levels of bone-specific markers ALP, RUNX2, and BMP2, as well as those of SLC7A5 and c-MYC. Furthermore, SLC7A5 and c-MYC expression was evaluated via immunofluorescence. To elucidate the roles of SLC7A5 and c-MYC in osteoblast differentiation, cells were transfected with SLC7A5 or c-MYC siRNAs, or treated with the SLC7A5-specific inhibitor JPH203 and c-MYC-specific inhibitor 10058-F4, and the expression of SLC7A5, c-MYC, and bone-specific markers ALP, RUNX2, and BMP2 was assessed. Results: Our results demonstrated that IL-18 increased calcium deposition in hBMSCs, and upregulated the expression of SLC7A5, c-MYC, ALP, RUNX2, and BMP2. Silencing of SLC7A5 or c-MYC using siRNA reduced the expression of ALP, RUNX2, and BMP2, while IL-18 treatment partially reversed the inhibitory effect of siRNA. Similar results were obtained by treating hBMSCs with SLC7A5 and c-MYC specific inhibitors, leading to significant reduction of the osteogenesis effect of IL-18 on hBMSCs. Conclusion: In conclusion, our results indicate that IL-18 promotes the osteogenic differentiation of hBMSCs via the SLC7A5/c-MYC pathway and, therefore, may play an important role in fracture healing. These findings will provide new treatment strategies for delayed fracture healing after splenectomy.
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影响因子：
7.5
作者：
Gibon E;Lu L;Goodman SB
通讯作者：
Goodman SB
影响因子：
4
作者：
Apalset, E. M.;Gjesdal, C. G.;Tell, G. S.
通讯作者：
Tell, G. S.
影响因子：
5.4
作者：
Fu, Zhaozong;Liu, Peng;Jiang, Jianming
通讯作者：
Jiang, Jianming
影响因子：
11.1
作者：
Chan JK;Glass GE;Ersek A;Freidin A;Williams GA;Gowers K;Espirito Santo AI;Jeffery R;Otto WR;Poulsom R;Feldmann M;Rankin SM;Horwood NJ;Nanchahal J
通讯作者：
Nanchahal J
DOI：
10.4049/jimmunol.1301542
发表时间：
2015-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Gandhapudi SK;Tan C;Marino JH;Taylor AA;Pack CC;Gaikwad J;Van De Wiele CJ;Wren JD;Teague TK
通讯作者：
Teague TK