Radiotherapy-induced bone deterioration is exacerbated in diabetic rats treated with streptozotocin.
Radiotherapy-induced bone deterioration is exacerbated in diabetic rats treated with streptozotocin.
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接受链脲佐菌素治疗的糖尿病大鼠会加剧放疗引起的骨质恶化
DOI：
10.1590/1414-431x2021e11550
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Cai J
中科院分区：
文献类型：
--
作者：
Jiang M;Ding Y;Xu S;Hao X;Yang Y;Luo E;Jing D;Yan Z;Cai J
放疗后，患者骨量减少，脆性骨折风险增加。据报道，糖尿病（DM）对骨结构和骨质量也有不利影响。然而，没有临床或实验研究系统地描述了糖尿病患者放疗后的骨表型。注射链脲佐菌素1个月后，对3月龄雄性大鼠进行局灶放疗（8 Gy， 2次，第1天和第3天），照射2个月后评估骨量、微结构、周转率和骨细胞活性。显微计算机断层扫描结果显示，与DM或放疗引起的骨结构损伤相比，DM大鼠在照射后表现出更大的骨小梁骨量和微结构的恶化。血清生化、骨组织形态学和基因表达分析显示，与DM或单独放疗相比，DM联合放疗的骨形成率、骨表面成骨细胞数量以及成骨相关标志物（ALP、Runx2、Osx、Col-1）的表达均较低。与DM或单独照射相比，DM加照射也能引起更高的骨吸收率、骨表面破骨细胞数量和破骨细胞特异性标志物（TRAP、cathepsin K和降钙素受体）的表达。此外，在DM和放疗联合治疗的大鼠中，观察到骨细胞存活率降低，Sost和DKK1基因（两种Wnt信号的负调节因子）表达升高。总之，这些发现揭示了放疗后糖尿病骨骼的更高恶化，并强调了健康维护的临床重要性。
Following radiotherapy, patients have decreased bone mass and increased risk of fragility fractures. Diabetes mellitus (DM) is also reported to have detrimental effects on bone architecture and quality. However, no clinical or experimental study has systematically characterized the bone phenotype of the diabetic patients following radiotherapy. After one month of streptozotocin injection, three-month-old male rats were subjected to focal radiotherapy (8 Gy, twice, at days 1 and 3), and then bone mass, microarchitecture, and turnover as well as bone cell activities were evaluated at 2 months post-irradiation. Micro-computed tomography results demonstrated that DM rats exhibited greater deterioration in trabecular bone mass and microarchitecture following irradiation compared with the damage to bone structure induced by DM or radiotherapy. The serum biochemical, bone histomorphometric, and gene expression assays revealed that DM combined with radiotherapy showed lower bone formation rate, osteoblast number on bone surface, and expression of osteoblast-related markers (ALP, Runx2, Osx, and Col-1) compared with DM or irradiation alone. DM plus irradiation also caused higher bone resorption rate, osteoclast number on bone surface, and expression of osteoclast-specific markers (TRAP, cathepsin K, and calcitonin receptor) than DM or irradiation treatment alone. Moreover, lower osteocyte survival and higher expression of Sost and DKK1 genes (two negative modulators of Wnt signaling) were observed in rats with combined DM and radiotherapy. Together, these findings revealed a higher deterioration of the diabetic skeleton following radiotherapy, and emphasized the clinical importance of health maintenance.