I am a
Home I AM A Search Login

Papers of the Week


Papers: 26 Oct 2024 - 1 Nov 2024


2024 Oct 19


Int J Mol Sci


39457038


25


20

Unraveling the Pathogenesis of Calcinosis in Systemic Sclerosis: A Molecular and Clinical Insight.

Authors

Avanoglu Guler A, De Luca G, Dagna L, Matucci-Cerinic M, Campochiaro C

Abstract

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.