Xu Xiaoya, Li Ruixia, Zhou Yi, Zou Qiong, Ding Qiaoling, Wang Jinfeng, Jin Weifang, Hua Guoqiang, Gao Jianjun
Department of Radiation Biology, Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai, 200032, China.
Obstetrics and Gynecology Hospital of Fudan University, No. 419 Fangxie Road, Shanghai, 200011, China.
Stem Cell Res Ther. 2017 Mar 20;8(1):71. doi: 10.1186/s13287-017-0527-0.
While it is known that irradiation can induce local and systemic bone loss over time, how focal irradiation induces systemic bone complications remains unclear. Immune cells are thought to be crucial to bone homeostasis, and abnormal immune cells lead to serious disruption of bone homeostasis, such as in acute lymphoblastic leukaemia. This disruption primarily occurs due to inhibition of the osteogenic differentiation of bone mesenchymal stem cells (BMSCs).
In this study, we detected local and systemic bone loss in trabecular bone by micro-computed tomography (micro-CT) and measurement of peroxisome proliferator-activated receptor gamma (PPARγ) and runt-related transcription factor 2 (RUNX2) expression in BMSCs using real-time polymerase chain reaction and western blotting. Additionally, changes in lymphocytes (B cells and CD4 and CD8 T cells) in the peripheral blood and bone marrow were analysed by flow cytometry. BMSC-derived osteoblasts and adipocytes, cultured in osteogenic or adipogenic media or co-cultured with lymphocytes, were detected by BCIP/NBT, Alizarin Red S and Oil Red O staining.
Focal irradiation induced local and systemic bone loss in trabecular bone. Increased PPARγ expression and decreased RUNX2 expression were observed, accompanied by upregulated adipogenesis and downregulated osteogenesis of BMSCs. B cells and CD8 T lymphocytes were increased in the blood and bone marrow after irradiation, while CD4 T lymphocytes were decreased in the blood. Inhibition of RUNX2 expression and reduction of alkaline phosphatase activity and mineralization deposits were observed in lymphocyte-co-cultured BMSCs, accompanied by an increase in PPARγ expression and in the number of lipid droplets.
Focal irradiation induced local and systemic bone loss in trabecular bone. Increased B cells and CD8 T lymphocytes led to systemic bone loss by decreasing BMSC osteogenesis.
虽然已知随着时间推移，辐射可导致局部和全身性骨质流失，但局部辐射如何引发全身性骨并发症仍不清楚。免疫细胞被认为对骨稳态至关重要，而异常免疫细胞会导致骨稳态严重破坏，如在急性淋巴细胞白血病中。这种破坏主要是由于骨间充质干细胞（BMSC）的成骨分化受到抑制。
在本研究中，我们通过显微计算机断层扫描（micro-CT）检测小梁骨中的局部和全身性骨质流失，并使用实时聚合酶链反应和蛋白质印迹法测量BMSC中过氧化物酶体增殖物激活受体γ（PPARγ）和 runt相关转录因子2（RUNX2）的表达。此外，通过流式细胞术分析外周血和骨髓中淋巴细胞（B细胞以及CD4和CD8 T细胞）的变化。使用BCIP/NBT、茜素红S和油红O染色检测在成骨或成脂培养基中培养或与淋巴细胞共培养的BMSC来源的成骨细胞和脂肪细胞。
局部辐射导致小梁骨局部和全身性骨质流失。观察到PPARγ表达增加和RUNX2表达降低，同时伴随着BMSC的成脂作用上调和成骨作用下调。照射后血液和骨髓中的B细胞和CD8 T淋巴细胞增加，而血液中的CD4 T淋巴细胞减少。在与淋巴细胞共培养的BMSC中观察到RUNX2表达受到抑制，碱性磷酸酶活性和矿化沉积物减少，同时PPARγ表达和脂滴数量增加。
局部辐射导致小梁骨局部和全身性骨质流失。B细胞和CD8 T淋巴细胞增加通过降低BMSC成骨作用导致全身性骨质流失。
