Kuroiwa Tomoyuki, Matsumoto Megumi, Kato Ryuji, Nimura Akimoto, Yoshii Toshitaka, Okawa Atsushi, Fujita Koji
Department of Orthopaedic and Spinal Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Laboratory of Cell and Molecular Bioengineering, Division of Biosciences, Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Room 302, Pharmaceutical Sciences Building Graduate School of Pharmaceutical Sciences, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan.
Bone Rep. 2019 Feb 21;10:100199. doi: 10.1016/j.bonr.2019.100199. eCollection 2019 Jun.
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 signaling . 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.
糖尿病是一种葡萄糖代谢疾病，它会对骨代谢产生不利影响，并增加癌症发生的风险。此前，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，我们试图研究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名非糖尿病个体。我们在骨科手术中从切除的股骨头中分离出人成熟成骨细胞，并提取其RNA。我们通过RNA微阵列和通路分析比较了两组之间的基因表达。微阵列分析显示两组之间19463个基因中的885个存在显著差异（p<0.05），通路分析显示糖尿病组中与癌症相关的通路和丝裂原活化蛋白激酶信号通路显著激活（p<0.01）。这些初步发现表明糖尿病会影响人成熟成骨细胞的细胞内信号传导，并且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，还可能与癌症代谢有关。我们计划进行进一步研究，以检查糖尿病成骨细胞中的信号传导，并进一步研究此处确定的基因和通路。
