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

105 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

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Osteoclasts
Interleukin-1
Macrophages
Microphthalmia-Associated Transcription Factor
Cytokines
RANK Ligand
Osteogenesis
Transcriptional Activation
Joints
Bone and Bones

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

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

The mechanism of osteoclast differentiation induced by IL-1. / Kim, Jung Ha; Jin, Hye Mi; Kim, Kabsun; Song, Insun; Youn, Bang Ung; Matsuo, Koichi; Kim, Nacksung.

In: Journal of Immunology, Vol. 183, No. 3, 01.08.2009, p. 1862-1870.

Research output: Contribution to journalArticle

Kim, JH, Jin, HM, Kim, K, Song, I, Youn, BU, Matsuo, K & Kim, N 2009, 'The mechanism of osteoclast differentiation induced by IL-1', Journal of Immunology, vol. 183, no. 3, pp. 1862-1870. https://doi.org/10.4049/jimmunol.0803007
Kim, Jung Ha ; Jin, Hye Mi ; Kim, Kabsun ; Song, Insun ; Youn, Bang Ung ; Matsuo, Koichi ; Kim, Nacksung. / The mechanism of osteoclast differentiation induced by IL-1. In: Journal of Immunology. 2009 ; Vol. 183, No. 3. pp. 1862-1870.
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