PMID- 18165223
OWN - NLM
STAT- MEDLINE
DCOM- 20080520
LR  - 20220309
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 283
IP  - 11
DP  - 2008 Mar 14
TI  - Interleukin-18 is regulated by parathyroid hormone and is required for its bone 
      anabolic actions.
PG  - 6790-8
LID - 10.1074/jbc.M709909200 [doi]
AB  - Interleukin-18 (IL-18) can regulate osteoblast and osteoclast function. We have 
      identified, using cDNA microarray technology, that IL-18 expression is increased 
      in UMR 106-01 rat osteoblastic cells in response to parathyroid hormone (PTH) 
      treatment. Confirmation of these data using real-time reverse transcription-PCR 
      showed that steady-state levels of IL-18 mRNA increased by 2 h (3-fold), peaked 
      by 4 h (10-fold), and had diminished after 12 h (4.4-fold) and that this 
      regulation was via the protein kinase A signaling pathway and did not involve 
      activation of the PKC signal cascade. PTH regulation of IL-18 was confirmed at 
      the protein level, and analysis of differentiating primary rat calvarial 
      osteoblasts verified that both IL-18 mRNA and protein are regulated by PTH in 
      primary rat osteoblasts. Promoter reporter assays revealed that PTH regulated the 
      upstream IL-18 promoter and induced the exon 1 containing 1.1-kb IL-18 mRNA 
      transcript in primary osteoblast cells. The in vivo physiological role of IL-18 
      in the anabolic actions of PTH on bone was then assessed using IL-18 knock-out 
      mice. Female IL-18 null mice and wild-type littermate controls were injected with 
      vehicle or 8 microg/100 g of human 1-38 PTH for 4 weeks. In IL-18 knock-out 
      animals the anabolic effect of PTH (determined by bone mineral density changes in 
      the proximal tibia) was abolished in trabecular bone but not in the cortical 
      component. These data characterize the PTH regulation of IL-18 expression in 
      osteoblastic cells and suggest that this cytokine is involved in the anabolic 
      actions of PTH.
FAU - Raggatt, Liza J
AU  - Raggatt LJ
AD  - Department of Physiology and Biophysics, University of Medicine and Dentistry of 
      New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
FAU - Qin, Ling
AU  - Qin L
FAU - Tamasi, Joseph
AU  - Tamasi J
FAU - Jefcoat, Stephen C Jr
AU  - Jefcoat SC Jr
FAU - Shimizu, Emi
AU  - Shimizu E
FAU - Selvamurugan, Nagarajan
AU  - Selvamurugan N
FAU - Liew, Foo Y
AU  - Liew FY
FAU - Bevelock, Laura
AU  - Bevelock L
FAU - Feyen, Jean H M
AU  - Feyen JH
FAU - Partridge, Nicola C
AU  - Partridge NC
LA  - eng
GR  - G9818261/MRC_/Medical Research Council/United Kingdom
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - DK48109/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20071228
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Interleukin-18)
RN  - 0 (Parathyroid Hormone)
SB  - IM
MH  - Animals
MH  - Bone and Bones/*metabolism
MH  - Female
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Interleukin-18/genetics/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Models, Biological
MH  - Models, Genetic
MH  - Osteoblasts/metabolism
MH  - Parathyroid Hormone/*metabolism
MH  - Promoter Regions, Genetic
MH  - Rats
EDAT- 2008/01/01 09:00
MHDA- 2008/05/21 09:00
CRDT- 2008/01/01 09:00
PHST- 2008/01/01 09:00 [pubmed]
PHST- 2008/05/21 09:00 [medline]
PHST- 2008/01/01 09:00 [entrez]
AID - S0021-9258(20)57115-9 [pii]
AID - 10.1074/jbc.M709909200 [doi]
PST - ppublish
SO  - J Biol Chem. 2008 Mar 14;283(11):6790-8. doi: 10.1074/jbc.M709909200. Epub 2007 
      Dec 28.