Punicalagin attenuates osteoclast differentiation by impairing NFATc1 expression and blocking Akt- and JNK-dependent pathways

Mayumi Iwatake, Kuniaki Okamoto, Takashi Tanaka, Takayuki Tsukuba

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Punicalagin is a bioactive polyphenol that is classified as an ellagitannin. Although punicalagin has been shown to have various pharmacological effects, such as anti-oxidative, anti-inflammatory, and anti-tumor effects, no studies have reported the effects of punicalagin on osteoclasts (OCLs). In this study, we investigated the effects of punicalagin on OCL differentiation by receptor activator of nuclear factor kappa-B ligand in the murine monocytic RAW-D cell line and bone marrow-derived macrophages (BMMs). Treatment with punicalagin significantly inhibited OCL formation from RAW-D cells and BMMs and prevented bone resorption of BMM-derived OCLs. Moreover, punicalagin impaired multinucleation and actin-ring formation in OCLs, and decreased the protein levels of nuclear factor of activated T cells cytoplasmic-1 (NFATc1), which is a master regulator of OCL differentiation, and concomitantly reduced the expression levels of Src and cathepsin K, which are transcriptionally regulated by NFATc1. The effects of punicalagin on intracellular signaling during the OCL differentiation of BMMs indicated that punicalagin-treated OCLs displayed markedly reduced phosphorylation of Jun N-terminal kinase and Akt, and partially impaired phosphorylation of extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and inhibitor of nuclear factor kappa-B alpha compared with untreated OCLs. Thus, punicalagin may affect bone metabolism by inhibiting OCL differentiation.

Original languageEnglish
Pages (from-to)161-172
Number of pages12
JournalMolecular and Cellular Biochemistry
Volume407
Issue number1-2
DOIs
Publication statusPublished - Sep 17 2015
Externally publishedYes

Fingerprint

NFATC Transcription Factors
MAP Kinase Signaling System
Osteoclasts
Bone
Macrophages
Phosphorylation
Somatostatin-Secreting Cells
punicalagin
Cathepsin K
RANK Ligand
Bone and Bones
NF-kappa B
Extracellular Signal-Regulated MAP Kinases
Polyphenols
p38 Mitogen-Activated Protein Kinases
Protein Kinase Inhibitors
Bone Resorption
Metabolism
Actins
Tumors

Keywords

  • NFATc1
  • Osteoclasts
  • Punicalagin

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Punicalagin attenuates osteoclast differentiation by impairing NFATc1 expression and blocking Akt- and JNK-dependent pathways. / Iwatake, Mayumi; Okamoto, Kuniaki; Tanaka, Takashi; Tsukuba, Takayuki.

In: Molecular and Cellular Biochemistry, Vol. 407, No. 1-2, 17.09.2015, p. 161-172.

Research output: Contribution to journalArticle

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