Visualizing bone tissue in homeostatic and pathological conditions

• Published in: Proceedings of the Japan Academy, Series B Vol. 96; no. 2; pp. 43 - 49
• Main Authors: HASEGAWA, Tetsuo, ISHII, Masaru
• Format: Journal Article
• Language: English
• Published: Japan The Japan Academy 10.02.2020
• Subjects: Acidification; Animals; Arthritis; Arthritis - metabolism; Behavior; Biomedical materials; Bone imaging; Bone marrow; Bone Marrow - diagnostic imaging; Bone Marrow - metabolism; Bone Resorption - diagnostic imaging; Bone Resorption - metabolism; Cell Differentiation; Fluorescent Dyes - chemistry; Fluorescent indicators; Homeostasis; Humans; imaging; Inflammation; macrophage; Macrophages; Macrophages - metabolism; Microscopy; Microscopy, Fluorescence, Multiphoton - methods; Optical Imaging - methods; Organic chemistry; Osteoblasts; osteoclast; Osteoclastogenesis; Osteoclasts; Osteoclasts - metabolism; Review; Sectioning; Synovium; Vitamin D; macrophage; arthritis; osteoclast; inflammation; imaging
• ISSN: 0386-2208; 1349-2896
• DOI: 10.2183/pjab.96.004

The human body is comprised of hundreds of bones, which are constantly regenerated through the interactions of two cell types: osteoblasts and osteoclasts. Given the difficulty of analyzing their intravital dynamics, we have developed a system for intravital imaging of the bone marrow cavity using two-photon microscopy, to visualize the dynamic behaviors of living bone cells without sectioning. Combined with the newly developed chemical fluorescent probes to detect localized acidification caused by osteoclasts, we identified two distinct functional states of mature osteoclasts, i.e., “bone-resorptive” and “non-resorptive”. Here, we focus on the dynamics and functions of bone cells within the bone marrow cavity and discuss how this novel approach has been applied to evaluate the mechanisms of action of drugs currently in clinical use. We further introduce our recent study that identified arthritis-associated osteoclastogenic macrophages in inflamed synovium and revealed their differentiation trajectory into the pathological osteoclasts, which together represent to a new paradigm in bone research.