Osteocyte Apoptosis Controls Activation of Intracortical Resorption in Response to Bone Fatigue
Osteocyte Apoptosis Controls Activation of Intracortical Resorption in Response to Bone Fatigue
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DOI：
10.1359/jbmr.081210
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发表时间：
2009-04-01
影响因子：
6.2
通讯作者：
Schaffler, Mitchell B.
中科院分区：
文献类型：
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作者：
Cardoso, Luis;Herman, Brad C.;Schaffler, Mitchell B.
骨细胞凋亡在空间和时间上与骨疲劳诱导的微损伤和随后的皮质内重塑有关。具体地说，骨疲劳微裂纹周围的骨细胞发生凋亡，这些地区含有凋亡的骨细胞共定位的领域，随后被破骨细胞吸收。在这里，我们测试的假设，骨细胞凋亡是一个关键的控制步骤，在激活和/或骨疲劳后骨吸收的目标。我们进行了体内疲劳负荷尺骨从4至5个月大的Sprague-Dawley大鼠处理与凋亡抑制剂（pancaspase抑制剂Q-V.D-OPh）或与车辆。在疲劳后第14天，通过标准组织形态计量学技术定量评估皮质内骨重建和骨细胞凋亡。连续暴露于Q-VD-OPh完全阻断了疲劳诱导的细胞凋亡和骨吸收的激活，而仅在疲劳后的前2天内短期抑制半胱天冬酶导致骨细胞凋亡和骨吸收减少>50%。这些结果（1）表明，骨细胞凋亡是必要的，以启动皮质内骨重建，以响应疲劳微损伤，（2）表明这两个过程之间可能存在剂量-反应关系，（3）表明，早期凋亡事件后，疲劳诱导的微损伤可能在决定组织重建的后续过程中发挥重要作用。
Osteocyte apoptosis is spatially and temporally linked to bone fatigue-induced microdamage and to subsequent intracortical remodeling. Specifically, osteocytes surrounding fatigue microcracks in bone undergo apoptosis, and those regions containing apoptotic osteocytes co-localize exactly with areas subsequently resorbed by osteoclasts. Here we tested the hypothesis that osteocyte apoptosis is a key controlling step in the activation and/or targeting of osteoclastic resorption after bone fatigue. We carried out in vivo fatigue loading of ulna from 4- to 5-mo-old Sprague-Dawley rats treated with an apoptosis inhibitor (the pancaspase inhibitor Q-V.D-OPh) or with vehicle. Intracortical bone remodeling and osteocyte apoptosis were quantitatively assessed by standard histomorphometric techniques on day 14 after fatigue. Continuous exposure to Q-VD-OPh completely blocked both fatigue-induced apoptosis and the activation of osteoclastic resorption, whereas short-term caspase inhibition during only the first 2 days after fatigue resulted in >50% reductions in both osteocyte apoptosis and bone resorption. These results (1) show that osteocyte apoptosis is necessary to initiate intracortical bone remodeling in response to fatigue microdamage, (2) indicate a possible dose-response relationship between the two processes, and (3) suggest that early apoptotic events after fatigue-induced microdamage may play a substantial role in determining the subsequent course of tissue remodeling.