Apoptotic bodies convey activity capable of initiating osteoclastogenesis and localized bone destruction
Apoptotic bodies convey activity capable of initiating osteoclastogenesis and localized bone destruction
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DOI：
10.1359/jbmr.080207
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发表时间：
2008-06-01
影响因子：
6.2
通讯作者：
Noble, Brendon S.
中科院分区：
文献类型：
--
作者：
Kogianni, Giolanta;Mann, Val;Noble, Brendon S.
前言：在体内，骨细胞凋亡与破骨细胞性骨吸收部位共定位，但这两个过程之间的因果分子或信号转导尚未确定。材料和方法：将MLO-Y4成骨样细胞来源的骨细胞凋亡体(OAbs)和原代小鼠成骨细胞来源的凋亡体(ABS)分别导入小鼠右侧顶骨，5天后观察破骨细胞性骨吸收情况。此外，在没有RANKL或巨噬细胞集落刺激因子的情况下，体外检测原代小鼠和细胞系来源的OAbs与小鼠骨髓造血祖细胞共同培养支持破骨细胞生成的能力。结果：我们首次证明OAbs能够在体内静止的骨表面启动新生的破骨细胞性骨吸收。此外，在体外向单核破骨细胞前体细胞(OPs)中加入OAbs后，OP细胞数量保持不变，TRACP(+)细胞比例和活性增加。相反，应用来自成骨细胞的ABS无论在体内还是在体外都没有显示出破骨活性。破骨细胞的成骨能力不依赖于已知的破骨细胞因子RANKL，但依赖于OP诱导的肿瘤坏死因子-α的产生。结论：这些数据提示死亡的骨细胞可能通过OAB相关信号的分布来靶向骨破坏，从而对骨的凋亡过程具有进一步的生理学意义。
Introduction: Osteocyte apoptosis co-localizes with sites of osteoclastic bone resorption in vivo, but to date, no causal molecular or signaling link has been identified between these two processes.Materials and Methods: Osteocyte apoptotic bodies (OABs) derived from the MLO-Y4 osteocyte-like cell line and primary murine osteocytes and apoptotic bodies (ABs) derived from primary murine osteoblasts were introduced onto the right parietal bone of murine calvariae, and osteoclastic bone resorption was examined 5 days after treatment. In addition, the ability of primary murine and cell line-derived OABs to support osteoclastogenesis was examined in vitro in co-culture with murine bone marrow hematopoietic progenitors in the absence of RANKL or macrophage-colony stimulating factor.Results: For the first time, we show that OABs are capable of initiating de novo osteoclastic bone resorption on quiescent bone surfaces in vivo. Furthermore, the addition of OABs to mononuclear osteoclast precursors (OPs) in vitro resulted in the maintenance of OP cell numbers and an increase in the proportion and activity of TRACP(+) cells. In contrast, application of ABs from osteoblasts showed no osteoclastogenic activity either in vivo or in vitro. The osteoclastogenic capacity of OABs was shown to be independent of the known osteoclastogenic factor RANKL but dependent on the induction of TNF-alpha production by OP.Conclusions: These data point to a mechanism by which dying osteocytes might target bone destruction through the distribution of OAB-associated signals and give further physiological meaning to the apoptotic process in bone.