Bcl-2, tissue transglutaminase and p53 protein expression in the apoptotic cascade in ribs of premature infants.
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.
Stevens
H Y
HY
Bone Research Group (MRC), Cambridge University, Department of Medicine, Addenbrooke's Hospital, UK.
Reeve
J
J
Noble
B S
BS
D017209:Apoptosis; D053938:DNA Fragmentation; D006132:Growth Plate / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism / Q000502:physiology*; D009252:NADPH Dehydrogenase / Q000032:analysis; D010006:Osteoblasts / Q000502:physiology; D010010:Osteoclasts / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D012272:Ribs; D011503:Transglutaminases / Q000032:analysis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D009252:NADPH Dehydrogenase; D011503:Transglutaminases