Activation of cancer-related and mitogen-activated protein kinase signaling pathways in human mature osteoblasts isolated from patients with type 2 diabetes

Abstract

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 in 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.