Activation of cancer-related and mitogen-activated protein kinase signaling pathways in human mature osteoblasts isolated from patients with type 2 diabetes.
Activation of cancer-related and mitogen-activated protein kinase signaling pathways in human mature osteoblasts isolated from patients with type 2 diabetes.
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从 2 型糖尿病患者分离的人类成熟成骨细胞中激活癌症相关和丝裂原激活蛋白激酶信号通路。
DOI：
10.1016/j.bonr.2019.100199
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Okawa A et al
中科院分区：
文献类型：
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作者：
Kuroiwa T;Yoshii T;Okawa A et al
糖尿病是一种葡萄糖代谢疾病，它对骨代谢产生不利影响，并增加癌症发展的风险。在此之前，我们报道了一种直接分离人成熟成骨细胞的方法，并指出成骨细胞与2型糖尿病相关的信号通路有关。此外，最近的一份报告表明，成骨细胞参与葡萄糖代谢。因此，我们试图在体内检测糖尿病对成骨细胞信号传导的影响。我们招募了8名2型糖尿病患者和8名非糖尿病患者。我们从骨科手术中切除的股骨头中分离出成熟的人成骨细胞，并提取其RNA。通过RNA微阵列和通路分析比较两组基因表达的差异。微阵列分析显示两组之间19，463个基因中的885个存在显著差异（p < 0.05），通路分析显示与癌症相关的通路和丝裂原活化蛋白激酶信号通路在糖尿病组中显著激活（p < 0.01）。这些初步研究结果表明，糖尿病影响人成熟成骨细胞的细胞内信号传导，成骨细胞可能不仅在骨和葡萄糖代谢的调节中起关键作用，而且可能与癌症代谢有关。我们计划进行进一步的研究，以检查糖尿病成骨细胞中的信号转导，并进一步研究这里确定的基因和途径。
Diabetes mellitus is a disease of glucose metabolism, and it adversely affects bone metabolism and increases the risk of cancer development. Previously, we reported a method for the direct isolation of human mature osteoblasts and indicated that osteoblasts were associated with type 2 diabetes mellitus-related signaling pathways. In addition, a recent report suggested that osteoblasts are involved in glucose metabolism. Thus, we sought to examine the effects of diabetes on osteoblast signalingin vivo. We recruited eight patients with type 2 diabetes and eight non-diabetic individuals. We isolated human mature osteoblasts from the resected femoral heads during orthopaedic surgery and extracted their RNA. We compared the gene expression between the two groups by RNA microarray and pathway analyses. Microarray analysis showed significant differences in 885 of 19,463 genes between the two groups (p < 0.05), and pathway analysis revealed that pathways related to cancer and the mitogen-activated protein kinase signaling pathway were significantly activated in the diabetes group (p < 0.01). These preliminary findings suggest that diabetes affects intracellular signaling in human mature osteoblasts and that osteoblasts might not only play a key role in the regulation of bone and glucose metabolism, but might also be related to cancer metabolism. We plan to conduct further studies to examine signaling in diabetic osteoblasts and to further investigate the genes and pathways identified here.