東北大学
学際科学フロンティア研究所

　Diabetes and osteoporosis are complex metabolic diseases and exist as chronic comorbidities with common regulatory pathways that converge genetically, as discovered by bivariate genome-wide association studies. Hyperglycemia is a hallmark of metabolic diseases and causes bone cell injury via reactive oxygen species (ROS) and advanced glycation end products (AGES). Hyperglycemia alters gene expression profiles impacting protein levels via dissociating transcription and translation. ROS and AGES can lead to aberrant modifications in RNA species and in protein structure and function. Bone is a signaling organ recognized for its role in regulating whole energy metabolism through osteokines, which are bone-derived factors. However, how bone cells interpret changes in energy fluctuation is currently unknown. Therefore, this project aims to decipher the “sweet bone phenomenon” without an a priori assumption using an integrative multi-omics analysis of molecular changes of bone cells existing in hyperglycemic conditions and prediabetes. We will provide a map of transcriptomic, epitranscriptomic, and proteomic changes using state-of-the-art modern omics analysis technologies and bioinformatics tools to discover novel study targets. This project will explore multiple layers and possible targets of the cell molecular machinery for future validation studies in animals and humans and will reveal possible markers of disease progression and drug development targets.