Osteocyte apoptosis regulates osteoclast precursor adhesion via osteocytic IL-6 secretion and endothelial ICAM-1 expression
Osteocyte apoptosis regulates osteoclast precursor adhesion via osteocytic IL-6 secretion and endothelial ICAM-1 expression
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DOI：
10.1016/j.bone.2011.09.052
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发表时间：
2012-01-01
期刊：
影响因子：
4.1
通讯作者：
You, Lidan
中科院分区：
文献类型：
--
作者：
Cheung, Wing-Yee;Simmons, Craig A.;You, Lidan
骨细胞的凋亡先于破骨细胞的吸收，可能是触发骨重建的关键信号。虽然已知破骨细胞前体通过循环传播，但它们在重塑部位聚集的具体机制尚不清楚。我们推测，骨细胞凋亡通过调节骨细胞分泌IL-6和可溶性IL-6受体(sIL-6R)促进内皮细胞ICAM-1表达，从而介导破骨细胞前体与血管内皮细胞的黏附。我们发现，由肿瘤坏死因子-α诱导的凋亡的MLO-Y4骨细胞的条件培养液促进RAW264.7破骨细胞前体与d4T内皮细胞的黏附(P<；0.05)。用泛半胱氨酸天冬氨酸氨基转移酶抑制剂(ZVAD-FMK)阻断骨细胞凋亡可降低破骨细胞前体黏附至基线水平(P<；0.001)。经凋亡性成骨细胞条件培养液处理的内皮细胞表面ICAM-1表达增加(P<；0.05)，阻断ICAM-1可抑制细胞凋亡诱导的破骨细胞前体黏附。凋亡性骨细胞条件培养液中IL-6(P<；0.05)和sIL-6R(P<；0.05)含量均高于非凋亡性骨细胞条件培养液。当外源性加入时，内皮细胞激活需要IL-6和sIL-6R，而阻断IL-6可减少由细胞凋亡诱导的破骨细胞前体黏附至基线水平(P<；0.05)。因此，我们得出结论：骨细胞凋亡可以通过ICAM-1促进破骨细胞前体与内皮细胞的黏附，这可能是通过增加骨细胞分泌IL-6和sIL-6R来实现的，而IL-6和sIL-6R是内皮细胞激活所必需的。(C)2011 Elsevier Inc.保留所有权利。
Osteocyte apoptosis precedes osteoclast resorption, and may act as a critical signal to trigger bone remodeling. While osteoclast precursors are known to travel via the circulation, the specific mechanisms by which they accumulate at remodeling sites are unclear. We hypothesized that osteocyte apoptosis mediates osteoclast precursor adhesion to vascular endothelium by regulating osteocytic secretion of IL-6 and soluble IL-6 receptor (sIL-6R) to promote endothelial ICAM-1 expression. We found that conditioned media from TNF-alpha-induced apoptotic MLO-Y4 osteocytes promoted RAW264.7 osteoclast precursor adhesion onto D4T endothelial cells (P < 0.05). Blocking osteocyte apoptosis with a pan-caspase inhibitor (ZVAD-FMK) reduced osteoclast precursor adhesion to baseline levels (P < 0.001). Endothelial cells treated with apoptotic osteocyte conditioned media had elevated surface expression of ICAM-1 (P < 0.05), and blocking ICAM-1 abolished apoptosis-induced osteoclast precursor adhesion. Apoptotic osteocyte conditioned media contained more IL-6 (P < 0.05) and sIL-6R (P < 0.05) than non-apoptotic osteocyte conditioned media. When added exogenously, both IL-6 and sIL-6R were required for endothelial activation, and blocking IL-6 reduced apoptosis-induced osteoclast precursor adhesion to baseline levels (P < 0.05). Therefore, we conclude that osteocyte apoptosis can promote osteoclast precursor adhesion to endothelial cells via ICAM-1; this is likely through increased osteocytic IL-6 and sIL-6R secretion, both of which are indispensible to endothelial activation. (C) 2011 Elsevier Inc. All rights reserved.