Abstract
Bone is a highly dynamic organ that is continuously being remodeled by the reciprocal interactions between bone and immune cells. We have originally established an advanced imaging system for visualizing the in vivo behavior of osteoclasts and their precursors in the bone marrow cavity using two-photon microscopy. Using this system, we found that the blood-enriched lipid mediator, sphingosine-1-phosphate, controlled the migratory behavior of osteoclast precursors. We also developed pH-sensing chemical fluorescent probes to detect localized acidification by bone-resorbing osteoclasts on the bone surface in vivo, and identified two distinct functional states of differentiated osteoclasts, “bone-resorptive” and “non-resorptive.” Here, we summarize our studies on the dynamics and functions of bone and immune cells within the bone marrow. We further discuss how our intravital imaging techniques can be applied to evaluate the mechanisms of action of biological agents in inflammatory bone destruction. Our intravital imaging techniques would be beneficial for studying the cellular dynamics in arthritic inflammation and bone destruction in vivo and would also be useful for evaluating novel therapies in animal models of bone-destroying diseases.
Highlights
The interdisciplinary research field focusing on the crosstalk between the bone and immune systems, termed “osteoimmunology,” has revealed extensive reciprocal interplay between the two systems [1,2,3]
We introduce our recent studies, including evaluation of the interaction between osteoclasts and osteoblasts, and our novel approach for evaluating the mechanisms of action of different biological agents used for the treatment of bone-destructive diseases
When macrophages enter a low-S1P environment, such as the bone marrow, S1PR1 is transported to the cell surface and osteoclast precursor macrophages move from bone tissue into the blood vessels, reflecting positive chemotaxis along an S1P gradient
Summary
The interdisciplinary research field focusing on the crosstalk between the bone and immune systems, termed “osteoimmunology,” has revealed extensive reciprocal interplay between the two systems [1,2,3]. The development of an intravital imaging system using two-photon microscopy, combined with an increasing variety of fluorescent reporter mouse strains and fluorescence probes, has provided insight into the dynamic behavior of osteoclasts, osteoblasts, macrophages, and T cells in the bone marrow of living mice. This approach facilitates investigation of cellular dynamics in the pathogenesis of osteoimmune diseases and enables direct observation of complex biological phenomena in vivo. We introduce our recent studies, including evaluation of the interaction between osteoclasts and osteoblasts, and our novel approach for evaluating the mechanisms of action of different biological agents used for the treatment of bone-destructive diseases
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