title: The expression of the nuclear matrix proteins NuMA, topoisomerase II-alpha, and -beta in bone and osseous cell culture: regulation by parathyroid hormone.
abstract: Bone cells undergo changes in cell structure during phenotypic development. Parathyroid hormone (PTH) induces a change in osteoblast shape, a determinant of collagen expression. We hypothesize that alterations in bone cell shape reflect and direct gene expression as governed, in part, by nuclear organization. In this study, we determined whether the expression of nuclear matrix proteins that mediate nuclear architecture, NuMA, topoisomerase II (topo II)-alpha, and -beta, were altered during osteoblast development and response to PTH in vivo. NuMA forms an interphase nuclear scaffold in some cells, the absence of which may accommodate alterations in nuclear organization necessary for specific functions. Topo II enzymes are expressed in bone cells; the alpha-isoform is specific to proliferating cells. We used immunohistochemistry 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 or with PTH treatment. NuMA and topo II-beta were expressed in marrow cells, osteoblasts, osteocytes, and chondrocytes. These proteins were not detected in osteoclasts in vivo, but were observed in cultured cells. Bone marrow cells expressed topo II-alpha. All three proteins were expressed in cultures of rat osteoblast-like UMR-106 cells. PTH treatment downregulated the number 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 vivo, nuclear matrix composition is altered during bone cell development and that anabolic doses of PTH attenuate the proliferative capacity of osteogenic cells, in part, by targeting topo II-alpha expression.
authors.affiliation: Department of Anatomy, Indiana University School of Medicine, Indianapolis, USA.
authors.forename: H A
authors.initials: HA
authors.lastname: Feister
authors.forename: J E
authors.initials: JE
authors.lastname: Onyia
authors.forename: R R
authors.initials: RR
authors.lastname: Miles
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.forename: R
authors.initials: R
authors.lastname: Galvin
authors.forename: J M
authors.initials: JM
authors.lastname: Hock
authors.forename: J P
authors.initials: JP
authors.lastname: Bidwell
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm; D034961:Antigens, Nuclear; D001842:Bone and Bones / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000951:Antigens, Neoplasm; D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D009687:Nuclear Proteins; C489081:Numa1 protein, rat; D010281:Parathyroid Hormone; D004250:DNA Topoisomerases, Type II