Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation

Sun Uk Bak, Suji Kim, Hae Jun Hwang, Jung A. Yun, Wan Sung Kim, Moo Ho Won, Ji Yoon Kim, Kwon Soo Ha, Young Guen Kwon, Young Myeong Kim

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Heme oxygenase (HO-1) catalyzes heme to carbon monoxide (CO), biliverdin/bilirubin, and iron and is known to prevent the pathogenesis of several human diseases. We assessed the beneficial effect of heme degradation products on osteoclastogenesis induced by receptor activator of NF-κB ligand (RANKL). Treatment of RAW264.7 cells with CORM-2 (a CO donor) and bilirubin, but not with iron, decreased RANKLinduced osteoclastogenesis, with CORM-2 having a more potent anti-osteogenic effect. CORM-2 also inhibited RANKLinduced osteoclastogenesis and osteoclastic resorption activity in marrow-derived macrophages. Treatment with hemin, a HO-1 inducer, strongly inhibited RANKL-induced osteoclastogenesis in wild-type macrophages, but was ineffective in HO-1+/- cells. CORM-2 reduced RANKL-induced NFATc1 expression by inhibiting IKK-dependent NF-κB activation and reactive oxygen species production. These results suggest that CO potently inhibits RANKL-induced osteoclastogenesis by inhibiting redox-sensitive NF-κB-mediated NFATc1 expression. Our findings indicate that HO-1/CO can act as an antiresorption agent and reduce bone loss by blocking osteoclast differentiation.

Original languageEnglish
Pages (from-to)103-108
Number of pages6
JournalBMB reports
Volume50
Issue number2
DOIs
Publication statusPublished - 2017

Bibliographical note

Funding Information:
This study is supported by 2015 Research Grant from Kangwon National University (No. 520150332) and by the National Research Foundation of Korea (NRF) Grant funded by the Korea Government (MSIP) (2013M3A9B6046563).

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

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