Cell proliferation and apoptosis during fracture healing
Cell proliferation and apoptosis during fracture healing
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DOI：
10.1359/jbmr.2002.17.5.791
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发表时间：
2002-05-01
影响因子：
6.2
通讯作者：
Marsh, D
中科院分区：
文献类型：
--
作者：
Li, G;White, G;Marsh, D
本研究研究了小鼠股骨骨折模型骨折愈合过程中细胞增殖和细胞凋亡之间的关系。对用单平面外固定器固定的 30 只成熟雄性 CFLP 小鼠进行左股骨截骨术。在骨折后第2、4、8、16和24天处死六只动物进行检查。使用增殖细胞核抗原（PCNA）单克隆抗体进行免疫组织化学检查细胞增殖的定位。使用末端脱氧核苷酸转移酶（TdT）介导的脱氧尿苷三磷酸（dUTP）-生物素缺口末端标记（TUNEL）方法观察凋亡细胞。捕获每个特定时间样本的图像。对每个高倍视野的总愈伤组织面积、PCNA 和 TUNEL 阳性标记的细胞进行定量。在整个研究期间发现细胞增殖和凋亡同时存在。在骨折愈合的早期阶段（第 2-8 天），PCNA 阳性标记占主导地位，并在第 8 天达到峰值，TUNEL 阳性标记最少。在骨折愈合的后期（第 16-24 天），PCNA 表达在第 16 天下降，因为愈伤组织骨化和重塑在骨折部位内扩散，细胞凋亡是主要细胞活性，TUNEL 阳性标记在第 16 天达到峰值，并在第 24 天急剧下降。这些细胞活性通过骨折愈伤组织的变化反映出来，其中总愈伤组织面积持续增加到第 16 天，随后在第 24 天减少。这项研究表明，细胞增殖细胞凋亡和细胞凋亡是骨折修复过程中的耦合事件，细胞增殖在早期活跃，细胞凋亡在愈伤组织重塑阶段活跃。
This study investigated the relation between cell proliferation and apoptosis during fracture healing in a mouse femoral fracture model. Left femoral osteotomies were performed in 30 mature male CFLP mice immobilized with uniplanar external fixators. Six animals were killed on days 2, 4, 8, 16, and 24 postfracture for examination. Localization of cell proliferation was examined using immunohistochemistry with proliferating cell nuclear antigen (PCNA) monoclonal antibody. Apoptotic cells were visualized with the terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-biotin nick end-labeling (TUNEL) method. Images of each time-specific specimen were captured. The total callus area, the positively labeled cells by PCNA, and TUNEL per high-power field were quantified. Cell proliferation and apoptosis were found coexisting during the entire period of study. In the early phases of fracture healing (days 2-8), PCNA-positive labeling was predominant and peaked at day 8 and the TUNEL-positive labeling was minimal. In later stages of fracture healing (days 16-24), PCNA expression declined at day 16 as callus ossification and remodeling spread within the fracture site and apoptosis was the dominant cell activity with the TUNEL-positive labeling peaking at day 16 and declining sharply at day 24. These cell activities were reflected by the change of fracture callus, where there was a continuous increase in total callus area to day 16 and subsequent decrease at day 24. This study indicated that cell proliferation and apoptosis are coupled events during fracture repair, cell proliferation is active at the early stages, and apoptosis is active during the phase of callus remodeling.