Physiological calcification of soft tissues is a common occurrence in aging and various acquired and inherited disorders. sequence variations cause the calcification phenotype of pseudoxanthoma elasticum (PXE) as well as some cases of generalized arterial calcification of infancy, which is otherwise caused by defective ENPP1. is primarily expressed in the liver, which has given the impression that the liver is central to the pathophysiology of PXE/generalized arterial calcification of infancy. The emergence of inflammation as a contributor to the calcification in PXE suggested that peripheral tissues play a larger role than expected. In this study, we investigated whether bone marrow–derived ABCC6 contributes to the calcification in PXE. In mice, we observed prevalent mineralization in several lymph nodes and surrounding connective tissues and an extensive network of lymphatic vessels within vibrissae, a calcified tissue in mice. Furthermore, we found evidence of lymphangiogenesis in patients with PXE and mouse skin, suggesting an inflammatory process. Finally, restoring wild-type bone marrow in mice produced a significant reduction of calcification, suggesting that the liver alone is not sufficient to fully inhibit mineralization. With evidence that ABCC6 is expressed in lymphocytes, we suggest that the adaptative immune system and inflammation largely contribute to the calcification in PXE/generalized arterial calcification of infancy.

中文翻译：

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骨髓源性 ABCC6 是弹性假黄瘤异位钙化的重要调节因子

软组织的生理性钙化是衰老和各种后天和遗传性疾病中常见的现象。序列变异导致弹性假黄瘤 (PXE) 的钙化表型以及婴儿期全身动脉钙化的一些病例，否则这是由 ENPP1 缺陷引起的。主要在肝脏中表达，这给人的印象是肝脏是 PXE/婴儿期全身动脉钙化病理生理学的核心。炎症作为 PXE 钙化的一个促成因素的出现表明，外周组织发挥的作用比预期更大。在这项研究中，我们研究了骨髓来源的 ABCC6 是否有助于 PXE 的钙化。在小鼠中，我们观察到几个淋巴结和周围结缔组织以及触毛（小鼠的钙化组织）内广泛的淋巴管网络普遍矿化。此外，我们在 PXE 患者和小鼠皮肤中发现了淋巴管生成的证据，表明存在炎症过程。最后，恢复小鼠野生型骨髓可显着减少钙化，表明仅靠肝脏不足以完全抑制矿化。有证据表明 ABCC6 在淋巴细胞中表达，我们认为适应性免疫系统和炎症在很大程度上导致了 PXE/婴儿期全身动脉钙化的钙化。