Abstract

Osteoimmunology highlights the reciprocal interactions between the skeletal and immune systems. Over the past two decades, many molecules that link the two have been identified, including cytokines, receptors and transcription factors, leading to successful translation of research into therapeutic approaches to autoimmune diseases such as rheumatoid arthritis. The development of an intravital imaging system using multi-photon microscopy, combined with a variety of fluorescent probes and reporter mouse strains, has provided valuable insights into the real-time dynamics of osteoclasts and immune cells in the bone marrow. This technique is now applied to the synovial tissue of arthritic mice to investigate the pathogenesis of osteoimmune diseases and enables direct observation of complex biological phenomena in vivo. In addition, rapid progress in the next-generation sequencing technologies has provided important insights into the field of osteoimmunology through characterizing individual cells in the synovial microenvironment. Single-cell RNA sequencing (scRNA-seq) dissects cellular heterogeneity within a biological system and enables the identification of specific cells differentiating into mature osteoclasts within the previously defined “osteoclast precursor (OP)-containing population”. In this review, we will explain the cellular interactions and cytokine milieu involved in inflammatory bone destruction and update how the novel technologies, such as scRNA-seq and intravital imaging, have contributed to better understand the pathogenesis of bone destruction in arthritis.

中文翻译：

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体内骨和关节成像：关节炎中的病理性破骨细胞生成

摘要

骨免疫学强调骨骼系统和免疫系统之间的相互作用。在过去的二十年里，已经确定了许多将两者联系起来的分子，包括细胞因子、受体和转录因子，从而成功地将研究转化为治疗类风湿性关节炎等自身免疫性疾病的方法。使用多光子显微镜开发的活体成像系统，结合各种荧光探针和报告小鼠品系，为了解骨髓中破骨细胞和免疫细胞的实时动态提供了宝贵的见解。该技术现已应用于关节炎小鼠的滑膜组织，以研究骨免疫疾病的发病机制，并能够直接观察体内复杂的生物学现象. 此外，下一代测序技术的快速发展通过表征滑膜微环境中的单个细胞为骨免疫学领域提供了重要的见解。单细胞 RNA 测序 (scRNA-seq) 剖析生物系统内的细胞异质性，并能够识别在先前定义的“含有破骨细胞前体 (OP) 的群体”中分化为成熟破骨细胞的特定细胞。在这篇综述中，我们将解释炎症性骨破坏中涉及的细胞相互作用和细胞因子环境，并更新 scRNA-seq 和活体成像等新技术如何有助于更好地了解关节炎中骨破坏的发病机制。