Association of sustained ERK activity with integrin β3 induction during receptor activator of nuclear factor kappaB ligand (RANKL)-directed osteoclast differentiation

Hong Hee Kim, Woon Jae Chung, Soo Woong Lee, Pah Jin Chung, Jae Won You, Ho Jeong Kwon, Sakae Tanaka, Zang Hee Lee

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)


Osteoclast differentiation is a multi-step process that involves cell proliferation, commitment, and fusion. Some adhesion molecules, including integrin αvβ3, have been shown to have roles in osteoclast fusion. In the course of studying with pharmacologic agents known to inhibit protein tyrosine kinases of the Src family, we found that radicicol increased cell fusion during receptor activator of nuclear factor kappaB ligand (RANKL)-driven differentiation of osteoclasts at concentrations far below the ones shown to inhibit its targets in previous studies. Treatments of low doses of radicicol to RAW 264.7 cells that undergo osteoclastic differentiation in the presence of RANKL enhanced the RANKL-induced gene expression of integrin β3 without any effect on the expression of integrin αv, which was constitutively high. The cell surface level of integrin αvβ3 complexes was consequently augmented by radicicol. In addition, sustained ERK and MEK activation was observed in cells treated with both radicicol and RANKL. More importantly, modulation of ERK activity by the MEK inhibitor U0126 or the gene transduction of a constitutively active form of MEK resulted in a suppression and increment, respectively, of integrin β3 induction by RANKL. Our data indicate that sustained ERK activity is associated with integrin β3 induction and subsequent cell surface expression of the αvβ3 integrin complex, which may contribute to cell fusion during RANKL-directed osteoclastogenesis.

Original languageEnglish
Pages (from-to)368-377
Number of pages10
JournalExperimental Cell Research
Issue number2
Publication statusPublished - 2003 Oct 1

Bibliographical note

Funding Information:
The authors acknowledge the financial support of grants from the Ministry of Science and Technology, Korea and the Korea Science and Engineering Foundation through the Research Center for Proteineous Materials and the National Research Laboratory.

All Science Journal Classification (ASJC) codes

  • Cell Biology


Dive into the research topics of 'Association of sustained ERK activity with integrin β3 induction during receptor activator of nuclear factor kappaB ligand (RANKL)-directed osteoclast differentiation'. Together they form a unique fingerprint.

Cite this