Department of Physiological Sciences, Science Faculty, Stellenbosch University, Stellenbosch, South Africa.
Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Parow, South Africa.
J Biomed Sci. 2021 Mar 3;28(1):15. doi: 10.1186/s12929-021-00714-w.
Although rheumatoid arthritis affects 1% of the global population, the role of rheumatoid cachexia, which occurs in up to a third of patients, is relatively neglected as research focus, despite its significant contribution to decreased quality of life in patients. A better understanding of the cellular and molecular processes involved in rheumatoid cachexia, as well as its potential treatment, is dependent on elucidation of the intricate interactions of the cells involved, such as myoblasts, fibroblasts and macrophages. Persistent RA-associated inflammation results in a relative depletion of the capacity for regeneration and repair in the satellite cell niche. The repair that does proceed is suboptimal due to dysregulated communication from the other cellular role players in this multi-cellular environment. This includes the incomplete switch in macrophage phenotype resulting in a lingering pro-inflammatory state within the tissues, as well as fibroblast-associated dysregulation of the dynamic control of the extracellular matrix. Additional to this endogenous dysregulation, some treatment strategies for RA may exacerbate muscle wasting and no multi-cell investigation has been done in this context. This review summarizes the most recent literature characterising clinical RA cachexia and links these features to the roles of and complex communication between multiple cellular contributors in the muscle niche, highlighting the importance of a targeted approach to therapeutic intervention.
尽管类风湿关节炎影响了全球 1%的人口，但多达三分之一的患者会出现类风湿性恶病质，尽管它显著降低了患者的生活质量，但作为研究重点，其相对受到忽视。更好地理解类风湿性恶病质所涉及的细胞和分子过程，以及其潜在的治疗方法，取决于阐明所涉及的细胞（如成肌细胞、成纤维细胞和巨噬细胞）之间复杂的相互作用。持续性 RA 相关炎症导致卫星细胞龛中再生和修复能力相对耗竭。由于在这个多细胞环境中其他细胞角色的通讯失调，进行的修复是不理想的。这包括巨噬细胞表型的不完全转换，导致组织内持续存在促炎状态，以及成纤维细胞相关的细胞外基质动态控制失调。除了这种内源性失调外，一些 RA 的治疗策略可能会加剧肌肉消耗，而且在这种情况下还没有进行多细胞研究。这篇综述总结了最近描述临床 RA 恶病质的文献，并将这些特征与肌肉龛中多个细胞贡献者的角色和复杂通讯联系起来，强调了针对治疗干预的靶向方法的重要性。
