PARATHYROID-RESPONSIVE MODIFICATIONS IN THE NUCLEAR MATRIX OF ROS-17 2.8-RAT OSTEOSARCOMA CELLS/

PTH is a mediator of skeletal development and remodeling that influenc es gene expression in osteoblastic cells. It is well established that PTH modulates the activity of membrane-associated second messenger sig nal transduction pathways. In these studies we have addressed the pote ntial contribution of components of cell structure to the integration of PTH-related regulatory signals that influence the expression of bon e cell genes. Chronic treatment of ROS 17/2.8 rat osteosarcoma cells w ith PTH is accompanied by changes in gene expression that are at least in part transcriptionally controlled. To explore the involvement of n uclear architecture in PTH-responsive modifications in gene expression , we investigated changes in the nuclear matrix after PTH treatment. C onsistent with a role for the nuclear matrix in determining spatial or ganization and topology of chromatin as well as in the localization an d targeting of transcription factors, we observed PTH-associated chang es in a 200-kilodalton nuclear matrix protein in response to PTH. A si gnificant down-regulation of synthesis was observed when nuclear matri x proteins were resolved electrophoretically in two-dimensional gels. This protein was restricted to the nuclear matrix and was not detected in the chromatin or cytoskeletal cellular fractions. These alteration s in nuclear matrix proteins that occur after PTH treatment in osteosa rcoma cells were phenotype related. They did not occur in UMR-106 POL or H4 hepatoma cells. Our findings support a role for the nuclear matr ix in transducing PTH-mediated regulatory signals to facilitate the ex tent to which genes in osteoblasts are transcribed.