Okadaic acid stimulates the expression of receptor activator of nuclear factor-kappa B ligand (RANKL) in mouse osteoblastic cells

Kaya Yoshida, Hirohiko Okamura, Hiroyuki Morimoto, Toshihiko Nagata, Tatsuji Haneji

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Receptor activator of nuclear factor-κB ligand (RANKL) is a membrane-bound signal transducer responsible for differentiation and maintenance of osteoclasts. To investigate a possible relationship between the status of protein phosphorylation and the regulation of RANKL in osteoblasts, we examined the effects of okadaic acid, a potent inhibitor of protein phosphatases, on cultured mouse osteoblastic MC3T3-E1 cells. Okadaic acid increased the amounts of RANKL protein in a dose-dependent fashion, with the maximum effective concentration being 100 nM. Okadaic acid at 100 nM stimulated the expression of RANKL mRNA and protein in MC3T3-E1 cells in a time-dependent manner up to 3 h. Okadaic acid also stimulated the expression of the Cbfa1 protein, a transcription factor required for osteoblast differentiation, in a dose-dependent manner. Binding of nuclear proteins prepared from MC3T3-E1 cells to Cbfa1 consensus sequence increased in a time-dependent manner when the cells had been treated with 100 nM okadaic acid. A 200-fold excess of unlabelled Cbfa1 oligonucleotide completely inhibited the DNA-protein complex formation. Our study demonstrate that okadaic acid stimulate RANKL production in MC3T3-E1 cells, indicating that the serine/threonine protein phosphatases play an important role in the regulation of bone metabolism.

Original languageEnglish
Pages (from-to)126-132
Number of pages7
JournalBiomedical Research
Volume14
Issue number2
Publication statusPublished - Oct 2003
Externally publishedYes

Fingerprint

RANK Ligand
Okadaic Acid
Phosphoprotein Phosphatases
Osteoblasts
Proteins
Phosphorylation
Consensus Sequence
Osteoclasts
Cytoplasmic and Nuclear Receptors
Nuclear Proteins
Transducers
Metabolism
Oligonucleotides
Carrier Proteins
Bone
Transcription Factors
Ligands
Maintenance
Membranes
Bone and Bones

Keywords

  • Cbfa1
  • Okadaic acid
  • Osteoblast
  • Protein phosphatase
  • RANKL

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Okadaic acid stimulates the expression of receptor activator of nuclear factor-kappa B ligand (RANKL) in mouse osteoblastic cells. / Yoshida, Kaya; Okamura, Hirohiko; Morimoto, Hiroyuki; Nagata, Toshihiko; Haneji, Tatsuji.

In: Biomedical Research, Vol. 14, No. 2, 10.2003, p. 126-132.

Research output: Contribution to journalArticle

Yoshida, Kaya ; Okamura, Hirohiko ; Morimoto, Hiroyuki ; Nagata, Toshihiko ; Haneji, Tatsuji. / Okadaic acid stimulates the expression of receptor activator of nuclear factor-kappa B ligand (RANKL) in mouse osteoblastic cells. In: Biomedical Research. 2003 ; Vol. 14, No. 2. pp. 126-132.
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