Genetics, Genomics and Cancer Biology Ph.D. Program, Jefferson College of Life Sciences, Thomas Jefferson University, Philadelphia, PA, USA.
Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
J Bone Miner Res. 2023 Apr;38(4):457-463. doi: 10.1002/jbmr.4791. Epub 2023 Mar 13.
Ectopic calcification is characterized by inappropriate deposition of calcium mineral in nonskeletal connective tissues and can cause significant morbidity and mortality, particularly when it affects the cardiovascular system. Identification of the metabolic and genetic determinants of ectopic calcification could help distinguish individuals at the greatest risk of developing these pathological calcifications and could guide development of medical interventions. Inorganic pyrophosphate (PP ) has long been recognized as the most potent endogenous inhibitor of biomineralization. It has been intensively studied as both a marker and a potential therapeutic for ectopic calcification. Decreased extracellular concentrations of PP have been proposed to be a unifying pathophysiological mechanism for disorders of ectopic calcification, both genetic and acquired. However, are reduced plasma concentrations of PP a reliable predictor of ectopic calcification? This perspective article evaluates the literature in favor and against a pathophysiological role of plasma versus tissue PP dysregulation as a determinant of, and as a biomarker for, ectopic calcification. © 2023 American Society for Bone and Mineral Research (ASBMR).
异位钙化的特征是钙矿物质在非骨骼结缔组织中的不当沉积，可导致严重的发病率和死亡率，尤其是当它影响心血管系统时。异位钙化的代谢和遗传决定因素的鉴定可以帮助区分发生这些病理性钙化的风险最大的个体，并可以指导医疗干预措施的制定。无机焦磷酸酯 (PP) 长期以来一直被认为是最有效的内源性生物矿化抑制剂。它被作为异位钙化的标志物和潜在的治疗药物进行了深入研究。已经提出细胞外 PP 浓度降低是遗传和获得性异位钙化紊乱的统一病理生理机制。然而，血浆中 PP 浓度降低是否是异位钙化的可靠预测因子？本文从正反两方面评估了支持和反对血浆与组织 PP 失调作为异位钙化决定因素和生物标志物的文献。 2023 年美国骨骼与矿物质研究协会（ASBMR）。
