PARATHYROID-HORMONE REGULATES THE EXPRESSION OF RAT OSTEOBLAST AND OSTEOSARCOMA NUCLEAR MATRIX PROTEINS

Parathyroid hormone (PTH) alters osteoblast morphology. How these chan ges in cell shape modify nuclear structure and ultimately gene express ion is not known. Chronic exposure to rat PTH (1-34) [10 nM] attenuate d the expression of 200, 190, and 160 kD proteins in the nuclear matri x-intermediate filament subfraction of the rat osteosarcoma cells, ROS 17/2.8 [Bidwell et al. (1994b): Endocrinology 134:1738-1744]. Here, w e determined that these same PTH-responsive proteins were expressed in rat metaphyseal osteoblasts. We identified the 200 kD protein as a no n-muscle myosin. Although the molecular weights, subcellular distribut ion, and half-lives of the 190 and 160 kD proteins were similar to top oisomerase II-alpha and -beta, nuclear matrix enzymes that mediate DNA topology, the 190 and 160 kD proteins did not interact with topoisome rase antibodies. Nevertheless, the expression of topoisomerase II-alph a, and NuMA, a component of the nuclear core filaments, was also regul ated by PTH in the osteosarcoma cells. The 190 kD protein was selectiv ely expressed in bone cells as it was not observed in OK opossum kidne y cells, H4 hepatoma cells, or NIH3T3 cells. PTH attenuated mRNA expre ssion of the PTH receptor in our cell preparations. These results demo nstrate that PTH selectively alters the expression of osteoblast membr ane, cytoskeletal, and nucleoskeletal proteins. Topoisomerase II-alpha , NuMA, and the 190 and 160 kD proteins may direct the nuclear PTH sig nalling pathways to the target genes and play a structural role in ost eoblast gene expression. (C) 1996 Wiley-Liss, Inc.