The expression of the nuclear matrix proteins NuMA, topoisomerase II-alpha, and -beta in bone and osseous cell culture: Regulation by parathyroid hormone

Bone cells undergo changes in cell structure during phenotypic development. Parathyroid hormone (PTH) induces a change in osteoblast shape, a determin ant of collagen expression, We hypothesize that alterations in bone cell sh ape reflect and direct gene expression as governed, in part, by nuclear org anization, In this study, we determined whether the expression of nuclear m atrix proteins that mediate nuclear architecture, NuMA, topoisomerase II (t opo II)-alpha, and -beta, were altered during osteoblast development and re sponse to PTH in vivo. NuMA forms an interphase nuclear scaffold in some te lls, the absence of which may accommodate alterations in nuclear organizati on necessary for specific functions, Topo II enzymes are expressed in bone cells; the alpha-isoform is specific to proliferating cells. We used immuno histochemistry and flow cytometry to determine whether NuMA is expressed in the primary spongiosa of the rat metaphyseal femur and whether expression of NuMA? topo II-alpha, and II-beta changes during osteoblast development o r with PTH treatment. NuMA and topo II-beta were expressed in marrow cells, osteoblasts, osteocytes, and chondrocytes. These proteins were not detecte d in osteoclasts in vivo, but mere observed in cultured cells. Bone marrow cells expressed topo II-alpha. All three proteins were expressed in culture s of rat osteoblast-like UMR-106 cells. PTH treatment downregulated the num ber of topo II-alpha-immunopositive cells, correlated with a decrease in S- phase cells, in both bone tissue and cell culture, We conclude that, in viv o, nuclear matrix composition is altered during bone cell development and t hat anabolic doses of PTB attenuate the proliferative capacity of osteogeni c cells, in part, by targeting topo II-alpha expression, (C) 2000 by Elsevi er Science Inc. All rights reserved.