Bcl-2, tissue transglutaminase and p53 protein expression in time apoptotic cascade in ribs of premature infants

Apoptotic cells of the human growth plate have not previously been demonstr ated in situ. We have investigated the distribution of apoptotic cells in c ostosternal growth plates and bone of premature infants aged 4-11 d with a gestational age of similar to 26 wk. In addition, we investigated the immun olocalisation of apoptosis-related proteins within the growth plates and as sociated bone. A proportion of late hypertrophic chondrocytes and osteocyte s within newly formed primary spongiosa showed evidence of highly fragmente d DNA. The incidence of osteocyte apoptosis decreased as the distance from the chondroosseous junction increased. Tissue transglutaminase (tTG) expres sion was associated with apoptosis of osteocytes and hypertrophic chondrocy tes. In contrast the presence of tTG was demonstrated in osteoblasts and bo ne Lining cells but it did not colocalise with evidence of apoptosis. The a nti-apoptotic gene product Bcl-2 was absent from the growth plate but was p resent in osteocytes. Visual assessment indicated a greater occurrence of t he protein in cells occupying regions of low apoptosis. P53 was not demonst rated in the growth plate or bone. These findings would indicate that human growth plate chondrocytes appear to show little provision for ensuring cel l longevity. In contrast osteocyte apoptosis appears negatively correlated with the skeletal distribution of Bcl-2 protein in the human infant, implyi ng a potential selective vulnerability in individual cells. Lack of Bcl-2 a nd the high incidence of osteocyte apoptosis in the more rapidly remodellin g bone of the human infant suggest a potential role of osteocyte apoptosis in the remodelling process.