Interleukin-1β Suppresses the Transporter Genes Ank and Ent1 Expression in Stromal Progenitor Cells Retaining Mineralization
Interleukin-1β Suppresses the Transporter Genes Ank and Ent1 Expression in Stromal Progenitor Cells Retaining Mineralization
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DOI：
10.1007/s00223-016-0139-1
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发表时间：
2016-08-01
影响因子：
4.2
通讯作者：
Noda, Masaki
中科院分区：
文献类型：
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作者：
Ezura, Yoichi;Lin, Xin;Noda, Masaki
异位骨化（HO）在各种组织引起的临床问题。基质祖细胞的炎症反应可能参与其病因。先前的研究表明，包括IL-1 β在内的促炎细胞因子通过抑制外核苷酸焦磷酸酶/磷酸二酯酶-1基因（ENPP 1）的表达来增强人骨髓间充质干细胞（MSCs）的体外钙化。然而，尚未调查其他相关因素的可能作用。在这里，我们研究了细胞外焦磷酸盐和核苷的调节剂的表达，包括Enpp 1，Nt 5e，Ank，Enptds和Ent 1，检查各种结缔组织基质祖细胞，包括来自小鼠的骨髓基质细胞和滑膜来源的细胞，或来自人的骨髓MSC。与以前的研究一致，我们观察到成骨细胞标记基因的特征抑制IL-1 β在成骨培养20天。此外，我们观察到重要的转运蛋白基因Ank和Ent 1的表达减少，而Enpp 1和Nt 5e水平的改变在细胞类型中并不总是一致的。我们的研究结果表明，IL-1 β不仅抑制成骨细胞，而且抑制软组织钙化的负调节因子，包括基质祖细胞中的Ank和Ent 1，这可能有助于各种疾病中HO的机制。
Heterotopic ossification (HO) in various tissues evokes clinical problems. Inflammatory responses of the stromal progenitor cells may be involved in its etiology. Previous report indicated that pro-inflammatory cytokines including IL-1 beta enhanced the in vitro calcification of human mesenchymal stem cells (MSCs), by suppressing the expression of ectonucleotide pyrophosphatase/phosphodiesterase-1 gene (ENPP1). However, possible contribution of other related factors had not been investigated. Here, we investigated the expression of regulators of extracellular pyrophosphate and nucleosides including Enpp1, Nt5e, Ank, Enptds, and Ent1, examining various connective tissue stromal progenitor cells, including bone marrow stromal cells and synovium derived cells from mouse, or bone marrow MSCs from human. Consistent with previous studies, we observed characteristic suppression of the osteoblastic marker genes by IL-1 beta during the osteogenic culture for 20 days. In addition, we observed a reduced expression of the important transporter genes, Ank and Ent1, whereas the alteration in Enpp1 and Nt5e levels was not always consistent among the cell types. Our results suggest that IL-1 beta suppresses not only the osteoblastic but also the negative regulators of soft-tissue calcification, including Ank and Ent1 in stromal progenitor cells, which may contribute to the mechanisms of HO in various disorders.