PTH Differentially Regulates Expression of RANKL and OPG

Abstract

We conclude that (1) PTH significantly upregulates RANKL mRNA in primary bone marrow stromal osteoblasts with maximal sensitivity occurring late in osteoblast differentiation; (2) PTH inhibits OPG gene expression at all stages of osteoblast differentiation; and (3) changes in RANKL and OPG mRNA levels after exposure to PTH are associated with increased osteoclastogenesis as demonstrated by increased numbers of TRACP+ cells in cocultures. The results further suggest that the osteoclastogenic activity of PTH occurs primarily by suppression of OPG gene expression in early osteoblasts and elevation of RANKL gene expression in mature osteoblasts.