In vivo demonstration that parathyroid hormone and parathyroid hormone-related protein stimulate expression by osteoblasts of interleukin-6 and leukemia inhibitory factor.
We have previously reported that parathyroid hormone (PTH) and PTH related protein (PTHrP) stimulate expression of interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) in osteoblasts in vitro. In the current study, we have developed a model of hormone injection into the subcutaneous space overlying mouse parietal bones to demonstrate that similar processes occur in osteoblasts in vivo. Specifically, PTH and PTHrP 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 activate both adenyl cyclase and phospholipase C-dependent signal transduction 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 activates phospholipase C. These results confirm our previous in vitro studies and support the hypothesis that IL-6 and/or LIF are physiologically important mediators of at least some of the actions of PTH and PTHrP.
Pollock
J H
JH
Department of Orthopaedics, Case Western Reserve University, Cleveland, Ohio, USA.
Blaha
M J
MJ
Lavish
S A
SA
Stevenson
S
S
Greenfield
E M
EM
D000199:Actins / Q000032:analysis / Q000187:drug effects; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006131:Growth Inhibitors / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D015675:Osteocalcin / Q000032:analysis / Q000187:drug effects; D010281:Parathyroid Hormone / Q000819:agonists / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000494:pharmacology*; D013997:Time Factors
D000199:Actins; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D015675:Osteocalcin