Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University.
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine.
Proc Jpn Acad Ser B Phys Biol Sci. 2020;96(2):43-49. 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.
人体由数百块骨头组成，这些骨头通过两种细胞类型的相互作用不断再生：成骨细胞和破骨细胞。鉴于分析其活体动力学的难度，我们开发了一种使用双光子显微镜对骨髓腔进行活体成像的系统，无需切片即可可视化活骨细胞的动态行为。结合新开发的化学荧光探针来检测破骨细胞引起的局部酸化，我们确定了成熟破骨细胞的两种不同功能状态，即“骨吸收”和“非吸收”。在这里，我们重点研究骨髓腔内骨细胞的动力学和功能，并讨论这种新方法如何应用于评估目前临床使用的药物的作用机制。我们进一步介绍了我们最近的研究，该研究在发炎的滑膜中鉴定出与关节炎相关的破骨细胞生成巨噬细胞，并揭示了它们分化为病理性破骨细胞的轨迹，这共同代表了骨研究中的一个新范例。
