Stevens H Y, Reeve J, Noble B S
Bone Research Group (MRC), Cambridge University, Department of Medicine, Addenbrooke's Hospital, UK.
J Anat. 2000 Feb;196 ( Pt 2)(Pt 2):181-91. doi: 10.1046/j.1469-7580.2000.19620181.x.
Apoptotic cells of the human growth plate have not previously been demonstrated in situ. We have investigated the distribution of apoptotic cells in costosternal growth plates and bone of premature infants aged 4-11 d with a gestational age of approximately 26 wk. In addition, we investigated the immunolocalisation of apoptosis-related proteins within the growth plates and associated bone. A proportion of late hypertrophic chondrocytes and osteocytes within newly formed primary spongiosa showed evidence of highly fragmented DNA. The incidence of osteocyte apoptosis decreased as the distance from the chondroosseous junction increased. Tissue transglutaminase (tTG) expression was associated with apoptosis of osteocytes and hypertrophic chondrocytes. In contrast the presence of tTG was demonstrated in osteoblasts and bone lining cells but it did not colocalise with evidence of apoptosis. The anti-apoptotic gene product Bcl-2 was absent from the growth plate but was present in osteocytes. Visual assessment indicated a greater occurrence of the protein in cells occupying regions of low apoptosis. P53 was not demonstrated in the growth plate or bone. These findings would indicate that human growth plate chondrocytes appear to show little provision for ensuring cell longevity. In contrast osteocyte apoptosis appears negatively correlated with the skeletal distribution of Bcl-2 protein in the human infant, implying a potential selective vulnerability in individual cells. Lack of Bcl-2 and the high incidence of osteocyte apoptosis in the more rapidly remodelling bone of the human infant suggest a potential role of osteocyte apoptosis in the remodelling process.
此前尚未在原位证实人类生长板的凋亡细胞。我们研究了胎龄约26周、年龄4 - 11天的早产儿肋胸骨生长板和骨骼中凋亡细胞的分布。此外,我们还研究了生长板及相关骨骼中凋亡相关蛋白的免疫定位。新形成的初级骨小梁内的一部分晚期肥大软骨细胞和骨细胞显示出高度碎片化DNA的证据。骨细胞凋亡的发生率随着与软骨骨连接距离的增加而降低。组织转谷氨酰胺酶(tTG)表达与骨细胞和肥大软骨细胞的凋亡相关。相比之下,在成骨细胞和骨衬细胞中证实了tTG的存在,但它与凋亡证据并不共定位。抗凋亡基因产物Bcl - 2在生长板中不存在,但在骨细胞中存在。视觉评估表明,在凋亡率低的区域的细胞中该蛋白的出现频率更高。在生长板或骨骼中未证实有P53。这些发现表明,人类生长板软骨细胞似乎很少有确保细胞寿命的机制。相比之下,人类婴儿中骨细胞凋亡似乎与Bcl - 2蛋白的骨骼分布呈负相关,这意味着单个细胞可能存在选择性易损性。人类婴儿中重塑较快的骨骼中缺乏Bcl - 2且骨细胞凋亡发生率高,表明骨细胞凋亡在重塑过程中可能发挥作用。