PARATHYROID-HORMONE INDUCES SEQUENTIAL C-FOS EXPRESSION IN BONE-CELLSIN-VIVO - IN-SITU LOCALIZATION OF ITS RECEPTOR AND C-FOS MESSENGER RIBONUCLEIC-ACIDS

Localization of PTH/PTH-related peptide (PTH/PTHrP) receptor mRNA and PTH induction of c-fos expression were examined in bones of 4-week-old rats by in situ hybridization. Receptor transcripts were most highly expressed by growth plate chondrocytes from lower proliferating to upp er hypertrophic cell layers. PTH/PTHrP receptor mRNA also was expresse d in osteoblasts as well as in some bone marrow stromal cells. Subcuta neous administration of human PTH-(1-84) (225 mu g/kg) induced rapid, transient, and sequential expression of the protooncogene c-fos mRNA i n cells in bone. Osteoblasts and chondrocytes expressing PTH/PTHrP rec eptor transcripts as well as some stromal cells expressed c-fos mRNA f irst (15-60 min), followed by transient expression in the majority of stromal cells and in osteoclasts (1-2 h). Delayed and transient induct ion of c-fos in cells with few or no detectable receptor transcripts s uggests that PTH acts indirectly on stromal cells and osteoclasts by e ither stimulating osteoblasts to secrete a substance(s) that acts loca lly and/or inducing changes in cell-cell contacts between osteoblasts and adjacent cells.