Topoisomerase II expression in osseous tissue

The molecular mechanisms that mediate the transition from an osteoprogenitor cell to a differentiated osteoblast are unknown. We propose that topoisomerase II (topo II) enzymes, nuclear proteins that mediate DNA topology, contribute to coordinating the loss of osteoprogenitor proliferative capacity with the onset of differentiation. The isoforms topo II‐α and ‐β, are differentially expressed in nonosseous tissues. Topo II‐α expression is cell cycle‐dependent and upregulated during mitogenesis. Topo II‐β is expressed throughout the cell cycle and upregulated when cells have plateaued in growth. To determine whether topo II‐α and ‐β are expressed in normal bone, we analyzed rat lumbar vertebrae using immunohistochemical staining. In the tissue sections, topo II‐α was expressed in the marrow cavity of the primary spongiosa. Mature osteoblasts along the trabecular surfaces did not express topo II‐α, but were immunopositive for topo II‐β, as were cells of the marrow cavity. Confocal laser scanning microscopy was used to determine the nuclear distribution of topo II in rat osteoblasts isolated from the metaphyseal distal femur and the rat osteosarcoma cells, ROS 17/2.8. Topo II‐α exhibited a punctate nuclear distribution in the bone cells. Topo II‐β was dispersed throughout the interior of the nucleus but concentrated at the nuclear envelope. Serum starvation of the cells attenuated topo II‐α expression but did not modulate expression of the β‐isoform. These results indicate that the loss of osteogenic proliferation correlates with the downregulation of topo II‐α expression. J. Cell. Biochem. 67:451–465, 1997. © 1997 Wiley‐Liss, Inc.