The mechanism of osteoclast differentiation induced by IL-1

Jung Ha Kim, Hye Mi Jin, Kabsun Kim, Insun Song, Bang Ung Youn, Koichi Matsuo, Nacksung Kim

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

IL-1 is a potent cytokine that can induce bone erosion in inflammatory sites such as rheumatoid joint regions via activation of osteoclasts. Not only is IL-1 capable of activating osteoclasts, but it is also a key cytokine involved in the differentiation, multinucleation, and survival of osteoclasts. Herein, we show that IL-1 has the potential to drive osteoclast differentiation via a receptor activator of NF-κB ligand (RANKL)/RANK-independent mechanism. Although IL-1 has a synergistic effect on RANKL-induced osteoclast formation, IL-1 alone cannot induce osteoclast differentiation from osteoclast precursors (bone marrow-derived macrophages (BMMs)) due to a lack of IL-1 signaling potential in these cells. However, we demonstrate that overexpression of the IL-1RI receptor in BMMs or induction of IL-1RI by c-Fos overexpression enables IL-1 alone to induce the formation of authentic osteoclasts by a RANKL/RANK-independent mechanism. The expression of IL-1RI is up-regulated by RANKL via c-Fos and NFATc1. Furthermore, the addition of IL-1 to IL-1RI overexpressing BMMs (IL-1/IL-1RI) strongly activates NF-κB, JNK, p38, and ERK which is a hallmark gene activation profile of osteoclastogenesis. Interestingly, IL-1/IL-1RI does not induce expression of c-Fos or NFATc1 during osteoclast differentiation, although basal levels of c-Fos and NFATc1 seem to be required. Rather, IL-1/IL-1RI strongly activates MITF, which subsequently induces osteoclast-specific genes such as osteoclast-associated receptor and tartrate-resistant acid phosphatase. Together, these results reveal that IL-1 has the potential to induce osteoclast differentiation via activation of microphthalmia transcription factor under specific microenvironmental conditions.

Original languageEnglish
Pages (from-to)1862-1870
Number of pages9
JournalJournal of Immunology
Volume183
Issue number3
DOIs
Publication statusPublished - 2009 Aug 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'The mechanism of osteoclast differentiation induced by IL-1'. Together they form a unique fingerprint.

  • Cite this

    Kim, J. H., Jin, H. M., Kim, K., Song, I., Youn, B. U., Matsuo, K., & Kim, N. (2009). The mechanism of osteoclast differentiation induced by IL-1. Journal of Immunology, 183(3), 1862-1870. https://doi.org/10.4049/jimmunol.0803007