Centre of Marine Sciences, University of Algarve, 8005-139 Faro, Portugal.
Faculty of Medicine and Biomedical Sciences, University of Algarve, 8005-139 Faro, Portugal.
Int J Mol Sci. 2023 Feb 8;24(4):3366. doi: 10.3390/ijms24043366.
Ectopic calcification refers to the pathological accumulation of calcium ions in soft tissues and is often the result of a dysregulated action or disrupted function of proteins involved in extracellular matrix mineralization. While the mouse has traditionally been the go-to model organism for the study of pathologies associated with abnormal calcium deposition, many mouse mutants often have exacerbated phenotypes and die prematurely, limiting the understanding of the disease and the development of effective therapies. Since the mechanisms underlying ectopic calcification share some analogy with those of bone formation, the zebrafish ()-a well-established model for studying osteogenesis and mineralogenesis-has recently gained momentum as a model to study ectopic calcification disorders. In this review, we outline the mechanisms of ectopic mineralization in zebrafish, provide insights into zebrafish mutants that share phenotypic similarities with human pathological mineralization disorders, list the compounds capable of rescuing mutant phenotypes, and describe current methods to induce and characterize ectopic calcification in zebrafish.
异位钙化是指钙离子在软组织中的病理性积累,通常是细胞外基质矿化相关蛋白作用失调或功能紊乱的结果。尽管小鼠一直是研究与异常钙沉积相关病理的首选模式生物,但许多小鼠突变体常表现出更为严重的表型,并过早死亡,这限制了对疾病的理解和有效治疗方法的发展。由于异位钙化的发生机制与骨形成的机制有些类似,斑马鱼()——一种研究成骨和矿化的成熟模型——最近作为研究异位钙化疾病的模型得到了重视。在这篇综述中,我们概述了斑马鱼异位矿化的机制,提供了与人类病理性矿化疾病具有相似表型的斑马鱼突变体的见解,列出了能够挽救突变表型的化合物,并描述了目前在斑马鱼中诱导和表征异位钙化的方法。