Vitamin D receptor: A critical regulator of inter-organ communication between skeletal and hematopoietic systems

The functions of vitamin D receptor (VDR) have been extensively studied, for example, in the bone biology field. It is widely known that VDR knockout mice display the characteristic features of rickets type II. However, the contribution of VDR signaling to bone marrow (BM) hematopoiesis in association with the phenomena observed in clinical hematology has not been evaluated thoroughly. Hematopoietic stem cells (HSCs) can be mobilized from the BM into and harvested from peripheral blood as a BM transplantation source for the curable treatment of hematologic malignancies. This HSC mobilization can be achieved by the administration of cytokine granulocyte colony-stimulating factor (G-CSF) for several consecutive days. We have reported that, using the murine model, G-CSF induces the high sympathetic tone in the BM and a β₂-adrenergic signal into osteoblasts induces a rapid and drastic increase of VDR, which is critical for the subsequent cascade for HSC mobilization. This is an example of the transient deviation of the inter-organ communication in three different systems (nervous, skeletal, and hematopoietic) bridged by VDR in osteoblasts. It would be important to reconsider VDR as a pivotal molecule that mediates inter-organ communication to broaden the application of vitamin D signal modulators.