IN-VIVO DEMONSTRATION THAT PARATHYROID-HORMONE AND PARATHYROID HORMONE-RELATED PROTEIN STIMULATE EXPRESSION BY OSTEOBLASTS OF INTERLEUKIN-6AND LEUKEMIA INHIBITORY FACTOR

We have previously reported that parathyroid hormone (PTH) and PTH rel ated protein (PTHrP) stimulate expression of interleukin-6 (IL-ti) and leukemia inhibitory factor (LIF) in osteoblasts in vitro, hi the curr ent study, we have developed a model of hormone injection into the sub cutaneous space overlying mouse parietal bones to demonstrate that sim ilar processes occur in osteoblasts in vivo, Specifically, PTH and PTH rP rapidly and transiently induce expression of the mRNAs encoding IL- 6 and LIF. The effects are dose-dependent, with a maximal stimulation of approximately 50-fold for each cytokine, Although PTH and PTHrP act ivate both adenyl cyclase and phospholipase G-dependent signal transdu ction pathways, stimulation of IL-6 and LIF depends on adenyl cyclase since it is not reproduced by PTH(3-34), a partial agonist that only a ctivates phospholipase C, These results confirm our previous in vitro studies and support the hypothesis that IL-6 and/or LIF are physiologi cally important mediators of at least some of the actions of PTH and P THrP.