Ruocco Anna, Sirico Anna, Novelli Rubina, Iannelli Silvia, Van Breda Shane Vontelin, Kyburz Diego, Hasler Paul, Aramini Andrea, Amendola Pier Giorgio
R&D, Dompé Farmaceutici SpA, Naples, Italy.
R&D, Dompé Farmaceutici SpA, Milan, Italy.
Front Cell Dev Biol. 2022 Aug 8;10:957800. doi: 10.3389/fcell.2022.957800. eCollection 2022.
Bone remodeling is a physiological, dynamic process that mainly depends on the functions of 2 cell types: osteoblasts and osteoclasts. Emerging evidence suggests that complement system is crucially involved in the regulation of functions of these cells, especially during inflammatory states. In this context, complement component 5a (C5a), a powerful pro-inflammatory anaphylatoxin that binds the receptor C5aR1, is known to regulate osteoclast formation and osteoblast inflammatory responses, and has thus been proposed as potential therapeutic target for the treatment of inflammatory bone diseases. In this review, we will analyze the role of C5a-C5aR1 axis in bone physiology and pathophysiology, describing its involvement in the pathogenesis of some of the most frequent inflammatory bone diseases such as rheumatoid arthritis, and also in osteoporosis and bone cancer and metastasis. Moreover, we will examine C5aR1-based pharmacological approaches that are available and have been tested so far for the treatment of these conditions. Given the growing interest of the scientific community on osteoimmunology, and the scarcity of data regarding the role of C5a-C5aR1 axis in bone pathophysiology, we will highlight the importance of this axis in mediating the interactions between skeletal and immune systems and its potential use as a therapeutic target.
骨重塑是一个生理动态过程，主要依赖于两种细胞类型的功能：成骨细胞和破骨细胞。新出现的证据表明，补体系统在这些细胞功能的调节中起着关键作用，尤其是在炎症状态下。在这种情况下，补体成分5a（C5a）是一种强大的促炎过敏毒素，可与受体C5aR1结合，已知其可调节破骨细胞形成和成骨细胞炎症反应，因此已被提议作为治疗炎症性骨病的潜在治疗靶点。在本综述中，我们将分析C5a - C5aR1轴在骨生理和病理生理中的作用，描述其在一些最常见的炎症性骨病（如类风湿性关节炎）以及骨质疏松症、骨癌和转移的发病机制中的作用。此外，我们将研究目前可用的且已针对这些病症进行测试的基于C5aR1的药理学方法。鉴于科学界对骨免疫学的兴趣日益浓厚，以及关于C5a - C5aR1轴在骨病理生理学中作用的数据稀缺，我们将强调该轴在介导骨骼与免疫系统相互作用中的重要性及其作为治疗靶点的潜在用途。
