Nature 458: 524-528 (2009)

Osteoclasts are bone-resorbing multinuclear giant cells that differentiate from mononuclear macrophage/monocyte-lineage hematopoietic precursors. They play critical roles not only in normal bone homeostasis, but also in the pathogenesis of bone destructive disorders such as rheumatoid arthritis and postmenopausal osteoporosis. We have developed a novel method for direct in situ visualization of cell behavior using intravital 2 photon imaging. The application of this new imaging technologies add a critical dynamic dimension to the analysis, transforming speculations derived from indirect observations into conclusions based on direct evidence. The major finding of my current study is that sphingosine-1-phosphate (S1P), a lipid mediator (chemokine) enriched in blood, controls the movement of osteoclast precursors between the blood and the bone surface. Moreover, the authors proposed a novel therapeutics against bone-resorptive disorders with FTY720, an S1P agonist being studied clinically as an immunosuppressant. (This work is supported by the Intramural Research Program of NIAID, NIH, and partly by the Human Frontier Science Program.)