I have elucidated new mechanisms of signal transduction pathways, such as the regulation of gene expression, and have further revealed that their disruption is related to lifestyle-related diseases, abnormal cell differentiation, and aging using mouse models.
Regulation of biological functions by nuclear vitamin D receptor (VDR)
I have established the world's first VDR knockout (KO) mice and elucidated diverse functions of vitamin D mediated by VDR4) 6) 11) 34)。
Mechanisms of gene expression regulation of bone and ligament ossification.
I have established the world's first ligament cell line14), and elucidated the regulatory mechanism of gene expression in ligaments, which have ossification potential but are normally strongly suppressed20). We also elucidated one aspect of the mechanism by which mechanical stimulation promotes osteoblast differentiation as the molecular basis for reduced bone formation in bedridden and other patients.23)
Elucidation of the regulatory mechanism of glucose and energy metabolism by bone
I have elucidated the novel molecular mechanism for the regulation of glucose metabolism by a bone-derived hormone (osteocalcin) 27) 30). These revealed that diabetes causes insulin resistance in bone, which increases the risk of osteoporosis, and that reduced bone resorption impairs the molecular activation of osteocalcin.
Regulation of biological functions regulated by SIRT7
We have elucidated that SIRT7, one of the NAD+-dependent deacylase sirtuins, regulates post-translational modifications of various transcription factors and enzymes, and controls glucose and lipid metabolism37) 44) 58), cognitive function46), inflammation50) 52), bone metabolism51), cartilage metabolism49), aging62), energy metabolism by brown fat63).