Unit of Rheumatology, Ankara Etlik City Hospital, 06010 Ankara, Turkey.
Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy.
Int J Mol Sci. 2024 Oct 19;25(20):11257. doi: 10.3390/ijms252011257.
Dystrophic calcinosis, which is the accumulation of insoluble calcified crystalline materials within tissues with normal circulating calcium and phosphorus levels, is a frequent finding in systemic sclerosis (SSc) and represents a major burden for patients. In SSc, calcinosis poses significant challenges in management due to the associated risk of severe complications such as infection, ulceration, pain, reduction in functional capacity and quality of life, and lack of standardized treatment choices. The exact pathogenesis of calcinosis is still unknown. There are multifaceted factors contributing to calcinosis development, including osteogenic differentiation of cells, imbalance between promoter and inhibitors of mineralization, local disturbance in calcium and phosphate levels, and extracellular matrix as a template for mineralization. Several pathophysiological changes observed in SSc such as ischemia, exacerbated production of excessive reactive oxygen species, inflammation, production of inflammatory cytokines, acroosteolysis, and increased extracellular matrix production may promote the development of calcinosis in SSc. Furthermore, mitochondrial dynamics, particularly fission function through the activity of dynamin-related protein-1, may have an effect on the dystrophic calcinosis process. In-depth investigations of cellular mechanisms and microenvironmental influences can offer valuable insights into the complex pathogenesis of calcinosis in SSc, providing potential targeting pathways for calcinosis treatment.
营养不良性钙化，即正常循环钙磷水平的组织内不可溶性钙化结晶物质的积累，在系统性硬化症（SSc）中很常见，是患者的主要负担。在 SSc 中，钙化由于感染、溃疡、疼痛、功能能力和生活质量下降以及缺乏标准化治疗选择等严重并发症的相关风险，在管理方面带来了重大挑战。钙化的确切发病机制尚不清楚。有多种因素导致钙化的发展，包括细胞成骨分化、矿化促进剂和抑制剂之间的失衡、局部钙和磷酸盐水平紊乱以及细胞外基质作为矿化模板。SSc 中观察到的几种病理生理变化，如缺血、过度产生的活性氧增加、炎症、炎性细胞因子的产生、肢端骨溶解和细胞外基质产生增加，可能会促进 SSc 中钙化的发展。此外，线粒体动力学，特别是通过 dynamin-related protein-1 的活性的分裂功能，可能对营养不良性钙化过程有影响。深入研究细胞机制和微环境影响可以为 SSc 中钙化的复杂发病机制提供有价值的见解，并为钙化治疗提供潜在的靶向途径。
