...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Cellular Physiology >The role of osteocyte apoptosis in cancer chemotherapy-induced bone loss
【24h】

The role of osteocyte apoptosis in cancer chemotherapy-induced bone loss

机译：骨细胞凋亡在癌症的作用化疗所致骨质疏松

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Intensive cancer chemotherapy leads to significant bone loss, the underlying mechanism of which remains unclear. The objective of this study was to elucidate mechanisms for effect of the commonly used anti-metabolite methotrexate (MTX) on osteocytes and on general bone homeostasis. The current study in juvenile rats showed that MTX chemotherapy caused a 4.3-fold increase in the number of apoptotic osteocytes in tibial metaphysis, which was accompanied by a 1.8-fold increase in the number of tartrate-resistant acid phosphatase-positive bone resorbing osteoclasts, and a 35% loss of trabecular bone. This was associated with an increase in transcription of the osteoclastogenic cytokines IL-6 (10-fold) and IL-11 (2-fold). Moreover, the metaphyseal bone of MTX-treated animals exhibited a 37.6% increase in the total number of osteocytes, along with 4.9-fold higher expression of the DMP-1 transcript. In cultured osteocyte-like MLO-Y4 cells, MTX treatment significantly increased caspase-3-mediated apoptosis, which was accompanied by the formation of plasma membrane-born apoptotic bodies and an increase in IL-6 (24-fold) and IL-11 (29-fold) mRNA expression. Conditioned media derived from MTX-treated MLO-Y4 cells was twice as strong as untreated media in its capacity to induce osteoclast formation in primary bone marrow osteoclast precursors. Thus, our in vivo and in vitro data suggested that MTX-induced apoptosis of osteocytes caused higher recruitment of DMP-1 positive osteocytes and increased osteoclast formation, which could contribute towards the loss of bone homeostasis in vivo.
机译：密集的癌症化疗导致显著骨质疏松,底层的机制仍不清楚。阐明机制的影响常用anti-metabolite甲氨蝶呤(MTX)骨细胞和骨内稳态。目前的研究在幼年大鼠显示MTX化疗导致增加4.3倍凋亡在胫骨骨细胞的数量干骨后端,伴随着1.8倍数量增加tartrate-resistant酸突起phosphatase-positive骨破骨细胞,和35%的骨小梁的损失。与转录的增加有关osteoclastogenic细胞因子il - 6(10倍)IL-11(2倍)。MTX-treated动物表现出增加了37.6%骨细胞的总数,以及4.9倍的高表达DMP-1成绩单。细胞,MTX治疗显著增加caspase-3-mediated细胞凋亡,这是伴随着等离子体的形成membrane-born凋亡的身体和增加il - 6(采样)和IL-11(交易量)mRNA表达式。MTX-treated MLO-Y4细胞是两倍强未经处理的媒体的诱导能力破骨细胞形成主要的骨髓破骨细胞前体。体外数据显示MTX-induced细胞凋亡引起的骨细胞更高的DMP-1招聘积极的骨细胞和破骨细胞增加形成,可以向作出贡献体内骨内稳态的损失。

著录项

相似文献

  • 外文文献
  • 中文文献
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号