RANKL-independent human osteoclast formation with APRIL, BAFF, NGF, IGF I and IGF II
RANKL-independent human osteoclast formation with APRIL, BAFF, NGF, IGF I and IGF II
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DOI：
10.1016/j.bone.2010.12.023
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发表时间：
2011-04-01
期刊：
影响因子：
4.1
通讯作者：
Athanasou, N. A.
中科院分区：
文献类型：
--
作者：
Hemingway, F.;Taylor, R.;Athanasou, N. A.
已经描述了破骨细胞生成的非经典途径，其中几种细胞因子能够替代RANKL。这些细胞因子数量很少，它们在病理性骨吸收中的作用尚未确定。我们已经确定了另外五种细胞因子，APRIL，BAFF，NGF，IGF I和IGF II，它们可以诱导RANKL非依赖性破骨细胞生成。所有五种细胞因子诱导破骨细胞分化和活化，形成大量能够吸收骨的TRAP（+）和VNR+多核细胞。形成的TRAP（+）多核细胞数量在MCSF + RANKL支持的数量的40-75%范围内。吸收水平与其他已知RANKL替代品TNF α、IL-6和TGF-β诱导的水平相似。加入护骨素（RANKL的内源性诱饵受体）表明，这种再吸收不依赖于RANKL。APRIL、BAFF、IGF和IGF Ⅱ在骨巨细胞瘤中均有表达。IGF I和IGF II在所有肿瘤样品的基质细胞群中表现出非常强的表达。这些数据表明，非典型破骨细胞生成在正常和病理性骨吸收中起作用。(C)2011 Elsevier Inc. All rights reserved.
Non-canonical pathways of osteoclastogenesis have been described in which several cytokines are able to substitute for RANKL. These cytokines are few in number and their role(s) in pathological bone resorption has not been ascertained. We have identified five additional cytokines, APRIL, BAFF, NGF, IGF I and IGF II, that can induce RANKL-independent osteoclastogenesis. All five cytokines induced both osteoclast differentiation and activation with respect to the formation of significant numbers of TRAP(+) and VNR+ multinucleated cells that were capable of resorbing bone. The number of TRAP(+) multinucleated cells that formed was in the range of 40-75% of that supported by MCSF plus RANKL Resorption was at a similar level to that induced by the other known RANKL substitutes TNF alpha, IL-6 and TGF-beta. The addition of osteoprotegrin, the endogenous decoy receptor of RANKL, revealed that this resorption was independent of RANKL. APRIL, BAFF, IGF land IGF II were found to be expressed in giant cell tumour of bone. IGF I and IGF II demonstrated very strong expression in the stromal cell population of all tumour samples. This data suggests that non-canonical osteoclastogenesis plays a role in both normal and pathological bone resorption. (C) 2011 Elsevier Inc. All rights reserved.