Phosphodiesterase inhibitors stimulate osteoclast formation via TRANCE/RANKL expression in osteoblasts: Possible involvement of ERK and p38 MAPK pathways

Masamichi Takami, Eun Sook Cho, Soo Young Lee, Ryutaro Kamijo, Mijung Yim

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Phosphodiesterases (PDEs) are enzymes that degrade intracellular cAMP. In the present study, 3-isobutyl-1-methylxanthine (IBMX) and pentoxifylline, PDE inhibitors, induced osteoclast formation in cocultures of mouse bone marrow cells and calvarial osteoblasts. These inhibitors induced the expression of the osteoclast differentiation factor, TNF-related activation induced cytokine (TRANCE, identical to RANKL, ODF, and OPGL), in calvarial osteoblasts. IBMX induced phosphorylation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) in osteoblasts. Induction of TRANCE expression by IBMX was partially suppressed by the inhibitors of protein kinase A (PKA), ERK, and p38 MAPK, suggesting that activation of ERK and p38 MAPK, as well as PKA, is involved in TRANCE expression by IBMX. Osteoblasts expressed PDE4, a PDE subtype, and rolipram, a selective inhibitor of PDE4, induced TRANCE expression. These results suggest that PDE4 is a key regulator of TRANCE expression in osteoblasts, which in turn controls osteoclast formation.

Original languageEnglish
Pages (from-to)832-838
Number of pages7
JournalFEBS Letters
Volume579
Issue number3
DOIs
StatePublished - 31 Jan 2005

Keywords

  • Cyclic adenosine monophosphate
  • Osteoblast
  • Osteoclast
  • Phosphodiesterase
  • TNF-related activation-induced cytokine

Fingerprint

Dive into the research topics of 'Phosphodiesterase inhibitors stimulate osteoclast formation via TRANCE/RANKL expression in osteoblasts: Possible involvement of ERK and p38 MAPK pathways'. Together they form a unique fingerprint.

Cite this