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.

中文翻译：

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在稳态和病理状态下可视化骨组织。

人体由数百个骨骼组成，这些骨骼通过两种细胞类型（成骨细胞和破骨细胞）的相互作用不断再生。鉴于难以分析它们的体内动态，我们开发了一种使用双光子显微镜对骨髓腔进行活体内成像的系统，以可视化活体骨细胞的动态行为而无需切片。结合新开发的化学荧光探针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“骨吸收性”和“非吸收性”。这里，我们将重点放在骨髓腔内骨细胞的动力学和功能上，并讨论如何将这种新方法用于评估目前在临床上使用的药物的作用机理。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了与关节炎相关的破骨细胞巨噬细胞，并揭示了它们在病理性破骨细胞中的分化轨迹，它们共同代表了骨研究的新范例。