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The most characteristic features in our laboratory is to establish a major new experimental method, such as "intravital 2-photon imaging of bone tissues in vivo", with which we have revealed a novel regulatory mechanism on osteoclastogenesis by controlling the movement of osteoclast precursors between blood and endosteum (Figure 1). In future this laboratory has two major goals described as follows:

First, one of the major research targets has been the bone biology, elucidating the complex system for bone homeostasis in vivo. We proposed an original concept that the regulation of migration and positioning of osteoclast precursors, e.g. by chemokines and lipid mediators, is a novel point of control for bone homeostasis, and is also a clinically relevant therapeutic target. In the future study, we will unravel the whole regulatory system in bone biology. As physician-scientists, we will try to develop the new remedy for treating bone resorptive disorders.

The other direction of our laboratory is the development of the novel imaging techniques and the application of this methodology to the elucidation of a wide array of biological phenomenon. We are planning to employ this new method to the visualization of the behaviors of various types of hematopoietic cells in the bone marrow to further clarify their modes of migration and differentiation in vivo. Bone marrow is important as a reservoir as well as a maturation site for neutrophils and monocytes, and also it has recently been proposed to have a special location ("niche") for maintaining pluripotent hematopoietic stem cells or leukemic stem cells. We have also been using our imaging technology to observe various tissues other than bone, including liver, lung, tumor etc. at the single cell level. Thus, the intravital imaging technology provides a rich spectrum of cellular movement and localization to analyze.

[Figure 1] In vivo imaging of bone tissues. Bone marrow spaces of LysM-EGFP transgenic mouse (left panel) and CSF1R-EGFP transgenic mouse (right panel) observed by intravital 2-photon microscopy for bone tissues are shown. Blood microvessels were visualized by injecting TexasRed-conjugated dextran (high molecular weight: up to 70kDa). Movies showing their dynamic movements are displayed in the original website of our laboratory. Scale bars represent 30μm.