Accumulation of hyaluronic acid in stromal cells modulates osteoclast formation by regulation of receptor activator of nuclear factor kappa-B ligand expression
Accumulation of hyaluronic acid in stromal cells modulates osteoclast formation by regulation of receptor activator of nuclear factor kappa-B ligand expression
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DOI：
10.1016/j.bbrc.2019.03.137
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发表时间：
2019-05-07
影响因子：
3.1
通讯作者：
Ariyoshi, Wataru
中科院分区：
文献类型：
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作者：
Nakao, Yuko;Hikiji, Hisako;Ariyoshi, Wataru
透明质酸(HA)在骨和软骨代谢中起着关键作用。本研究探讨HA蓄积对1α，25(OH)(2)D-3和地塞米松诱导的基质细胞核因子kappa-B受体激活剂(RANKL)表达的影响及其机制。透明质酸酶(HA‘ase)降解透明质酸可增强Lα、25(OH)(2)D-3和地塞米松刺激的ST2细胞RANKL的表达。SiRNA下调透明质酸合成酶2(HAS2)的表达也能刺激1α，25(OH)(2)D-3和地塞米松诱导的RANKL表达。细胞与骨髓细胞共培养的结果表明，1α，25(OH)(2)D-3和地塞米松诱导的RANKL在HA‘ase处理和HAS2 siRNA转染的ST2细胞中的表达被高相对分子质量HA的细胞所下调。相反，促进HAS2表达和HA合成的转化生长因子-β1可下调1α，25(OH)(2)D-3和地塞米松诱导的RANKL表达。有趣的是，HAS2基因的敲除增强了1α，25(OH)(2)D-3和地塞米松刺激的ST2细胞中维生素D受体(VDR)的表达和信号转导和转录激活因子3(STAT3)的磷酸化。这些结果表明，骨髓细胞中HA的蓄积可能通过调节VDR和STAT3信号通路而影响RANKL介导的破骨细胞支持活性。(C)2019 Elsevier Inc.保留所有权利。
Hyaluronic acid (HA) has a pivotal role in bone and cartilage metabolism. In this study, we investigated the effect and underlying mechanisms of HA accumulation on the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) induced by 1 alpha,25(OH)(2)D-3 and dexamethasone in stromal cells, which support osteoclastogenesis. Degradation of HA by hyaluronidase (HA'ase) treatment enhanced the expression of RANKL in ST2 cells stimulated with l alpha,25(OH)(2)D-3 and dexamethasone. Down-regulation of hyaluronan synthase 2 (HAS2) expression by siRNA also stimulated RANKL expression induced by 1 alpha,25(OH)(2)D-3 and dexamethasone. Results from a cell co-culture system with bone marrow cell showed that 1 alpha,25(OH)(2)D-3 and dexamethasone-induced RANKL expression in HA'ase treated- and HAS2 siRNA transfected-ST2 cells was down-regulated by treatment of cells with high molecular weight HA. In contrast, transforming growth factor-beta 1 (TGF-beta 1), which stimulates HAS2 expression and HA synthesis, down-regulated RANKL expression induced by 1 alpha,25(OH)(2)D-3 and dexamethasone. Interestingly, knockdown of has2 gene enhanced the expression of vitamin D receptor (VDR) and phosphorylation of signal transducers and activator of transcription 3 (STAT3) in ST2 cells stimulated by 1 alpha,25(OH)(2)D-3 and dexamethasone. These results indicate that accumulation of HA in bone marrow cells may affect RANKLmediated osteoclast-supporting activity via regulation of VDR and STAT3 signaling pathways. (C) 2019 Elsevier Inc. All rights reserved.