Osteocyte apoptosis is required for production of osteoclastogenic signals following bone fatigue in vivo.
Osteocyte apoptosis is required for production of osteoclastogenic signals following bone fatigue in vivo.
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DOI：
10.1016/j.bone.2014.03.049
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发表时间：
2014-07
期刊：
影响因子：
4.1
通讯作者：
Schaffler, Mitchell B.
中科院分区：
文献类型：
--
作者：
Kennedy, Oran D.;Laudier, Damien M.;Majeska, Robert J.;Sun, Hui B.;Schaffler, Mitchell B.
骨细胞凋亡在空间、时间和功能上与骨微损伤的清除和替换有关。最近我们发现，微损伤在损伤部位附近的两种骨细胞群中引起了不同的反应。直接靠近微损伤的骨细胞会发生凋亡，而位于凋亡群体附近的第二组骨细胞会上调破骨细胞信号分子的表达。在这项研究中，我们使用泛半胱天蛋白酶抑制剂QVD来验证骨细胞凋亡是疲劳损伤骨中原位骨细胞产生关键破骨信号的必要步骤。我们发现，基于实时PCR和免疫组织化学分析，疲劳后细胞凋亡标志物caspase-3以及破骨细胞生成蛋白RANKL和VEGF的表达增加，而RANKL拮抗剂OPG的表达减少。然而，当使用QVD抑制细胞凋亡时，这些基因表达的变化被完全阻断。这种对邻近非凋亡细胞产生促进组织重塑信号的凋亡依赖也发生在脑和心脏局灶性缺血性损伤的反应中，表明破骨细胞骨重塑遵循局部组织修复的共同范式。
Osteocyte apoptosis is spatially, temporally and functionally linked to the removal and replacement of microdamage in bone. Recently we showed that microdamage elicits distinct responses in two populations of osteocytes near the injury site. Osteocytes directly adjacent to microdamage undergo apoptosis, whereas there is a second group of osteocytes located adjacent to the apoptotic population that upregulate expression of osteoclastogenic signaling molecules. In this study we used the pan-caspase inhibitor QVD to test the hypothesis that osteocyte apoptosis is an obligatory step in the production of key osteoclastogenic signals by in situ osteocytes in fatigue-damaged bone. We found, based on real-time PCR and immunohistochemistry assays, that expression of the apoptosis marker caspase-3 as well osteoclastogenic proteins RANKL and VEGF were increased following fatigue, while expression of the RANKL antagonist OPG decreased. However, when apoptosis was inhibited using QVD, these changes in gene expression were completely blocked. This dependence on apoptosis for neighboring non-apoptotic cells to produce signals that promote tissue remodeling also occurs in response to focal ischemic injury in brain and heart, indicating that osteoclastic bone remodeling follows a common paradigm for localized tissue repair.
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影响因子：
4
作者：
Bidwell, Joseph P.;Yang, Jieping;Robling, Alexander G.
通讯作者：
Robling, Alexander G.
影响因子：
4.1
作者：
O'Brien, Charles A.;Nakashima, Tomoki;Takayanagi, Hiroshi
通讯作者：
Takayanagi, Hiroshi
DOI：
10.1097/01.wcb.0000084252.20114.be
发表时间：
2003-09-01
影响因子：
6.3
作者：
Katsman, D;Zheng, J;Carmichael, ST
通讯作者：
Carmichael, ST
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1083/jcb.201004096
发表时间：
2010-06-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Elliott MR;Ravichandran KS
通讯作者：
Ravichandran KS