Interleukin-18 is regulated by parathyroid hormone and is required for its bone anabolic actions

Raggatt, Liza-Jane, Qin, Ling, Tamasi, Joseph, Jefcoat, Jr., Stephen C., Shimizu, Emi, Selvamurugan, Nagarajan, Liew, Foo Y., Bevelock, Laura, Feyen, Jean H. M. and Partridge, Nicola C. (2008) Interleukin-18 is regulated by parathyroid hormone and is required for its bone anabolic actions. The Journal of Biological Chemistry, 283 11: 6790-6798. doi:10.1074/jbc.M709909200

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Author Raggatt, Liza-Jane
Qin, Ling
Tamasi, Joseph
Jefcoat, Jr., Stephen C.
Shimizu, Emi
Selvamurugan, Nagarajan
Liew, Foo Y.
Bevelock, Laura
Feyen, Jean H. M.
Partridge, Nicola C.
Title Interleukin-18 is regulated by parathyroid hormone and is required for its bone anabolic actions
Journal name The Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2008-03-14
Year available 2007
Sub-type Article (original research)
DOI 10.1074/jbc.M709909200
Open Access Status File (Publisher version)
Volume 283
Issue 11
Start page 6790
End page 6798
Total pages 9
Place of publication Bethesda, MD, U.S.A.
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Subject 0304 Medicinal and Biomolecular Chemistry
0601 Biochemistry and Cell Biology
1101 Medical Biochemistry and Metabolomics
Formatted abstract
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 μg/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.
Keyword Interleukin-18
Osteoblastic cells
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID G9818261
Institutional Status Non-UQ
Additional Notes First Published on December 28, 2007

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 26 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 06 Jan 2010, 19:44:13 EST by June Temby on behalf of Institute for Molecular Bioscience