IDENTIFICATION OF APOPTOTIC CHANGES IN OSTEOCYTES IN NORMAL AND PATHOLOGICAL HUMAN BONE

Previous work on bone growth and biomechanics suggests that osteocytes might sense the requirement for bone remodeling and signal to cells i n the basic multicellular unit that undertake this function, The prese nt study looked for evidence of apoptosis in human osteocytes in adult , pediatric, and pathological bone to compare these situations of diff ering levels of turnover and considered the possibility of a functiona l role for this death mechanism in bone modeling and remodeling, Apopt osis was identified in bone tissue by agarose gel electrophoresis of D NA (to demonstrate DNA ladders), In cryostat sections it was possible to visualize individual cells with fragmented DNA in situ using a modi fied nick translation technique (NT), In addition, visualization of ap optotic morphology was undertaken using light and electron microscopy, Adult femoral head and iliac crest bone showed no evidence of DNA lad ders and very small numbers of osteocytes with DNA fragmentation using NT, In contrast, samples of pediatric calvaria, adult heterotopic bon e, and osteophytes all displayed characteristic laddering of extracted DNA and showed evidence of potentially apoptotic osteocytes in situ u sing NT, In agreement with these findings, transmission electron micro scopy showed numbers of osteocytes in infant calvaria with advanced ch romatin condensation and cell shrinkage indicative of apoptosis, Since all three types of positive bone are involved in rapid matrix turnove r, apoptotic changes in human osteocytes in vivo might be related in g eneral terms to the modeling and remodeling activity level of the bone sampled, It was further found that the distribution of potentially ap optotic cells in the infant and pathological bone was anatomically non uniform, raising the intriguing possibility of a functional relationsh ip between bone turnover and the controlled cell death of osteocytes. (C) 1997 by Elsevier Science Inc.