Xiong Wen, Guo Xin, Cai Xianhua
The First School of Clinical Medicine, Southern Medical University, Guangdong, China.
Folia Histochem Cytobiol. 2021;59(3):187-194. doi: 10.5603/FHC.a2021.0020. Epub 2021 Sep 28.
This study aimed to investigate the effects of stromal cell-derived factor-1 (SDF-1) and activation of its receptor, chemokine receptor 4 (CXCR4), on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and the key signaling mechanisms involved in these effects.
BMSCs were treated with 100 μg/L SDF-1 and cultured in osteogenic medium for 7 days. RT-qPCR and western blotting were used to detect the protein and mRNA levels of Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), Runt-related transcription factor 2 (Runx2), and osteocalcin (OCN). Alizarin-red staining was used to detect the mineralization-inducing ability of the cells.
After BMSCs were treated with SDF-1, the levels of JAK2 mRNA, STAT3 mRNA, and protein phosphorylation increased, the number of mineralized nodules of BMSCs increased, and the osteogenic-differentiation ability was enhanced. In addition, after BMSCs were treated with an inhibitor of JAK2 phosphorylation, the levels of JAK2, STAT3, Runx2, and OCN decreased significantly, the number of mineralized nodules of BMSCs also decreased, and the osteogenic-differentiation ability decreased. The inhibition of CXCR4-treated BMSCs further confirmed that SDF-1/CXCR4 activated JAK2/STAT3 to regulate the osteogenic differentiation of BMSCs.
SDF-1/CXCR4 promoted the osteogenic differentiation of BMSCs through JAK2/STAT3 activation.
本研究旨在探讨基质细胞衍生因子-1（SDF-1）及其受体趋化因子受体4（CXCR4）的激活对骨髓间充质干细胞（BMSCs）成骨分化的影响，以及这些影响所涉及的关键信号机制。
用100μg/L SDF-1处理BMSCs，并在成骨培养基中培养7天。采用RT-qPCR和蛋白质印迹法检测Janus激酶2（JAK2）、信号转导及转录激活因子3（STAT3）、 runt相关转录因子2（Runx2）和骨钙素（OCN）的蛋白质和mRNA水平。采用茜素红染色检测细胞的矿化诱导能力。
用SDF-1处理BMSCs后，JAK2 mRNA、STAT3 mRNA水平及蛋白质磷酸化水平升高，BMSCs矿化结节数量增加，成骨分化能力增强。此外，用JAK2磷酸化抑制剂处理BMSCs后，JAK2、STAT3、Runx2和OCN水平显著降低，BMSCs矿化结节数量也减少，成骨分化能力下降。对CXCR4处理的BMSCs的抑制进一步证实，SDF-1/CXCR4激活JAK2/STAT3以调节BMSCs的成骨分化。
SDF-1/CXCR4通过激活JAK2/STAT3促进BMSCs的成骨分化。
