IL-23 is critical for induction of arthritis, osteoclast formation, and maintenance of bone mass

Iannis Adamopoulos, Marlowe Tessmer, Cheng Chi Chao, Sarvesh Adda, Dan Gorman, Mary Petro, Chuan Chu Chou, Robert H. Pierce, Wei Yao, Nancy E Lane, Drake Laface, Edward P. Bowman

Research output: Contribution to journalArticle

96 Scopus citations

Abstract

The role of IL-23 in the development of arthritis and bone metabolism was studied using systemic IL-23 exposure in adult mice via hydrodynamic delivery of IL-23 minicircle DNA in vivo and in mice genetically deficient in IL-23. Systemic IL-23 exposure induced chronic arthritis, severe bone loss, and myelopoiesis in the bone marrow and spleen, which resulted in increased osteoclast differentiation and systemic bone loss. The effect of IL-23 was partly dependent on CD4+ T cells, IL-17A, and TNF, but could not be reproduced by overexpression of IL-17A in vivo. A key role in the IL-23 - induced arthritis was made by the expansion and activity of myeloid cells. Bone marrow macrophages derived from IL-23p19-/- mice showed a slower maturation into osteoclasts with reduced tartrate-resistant acid phosphatase-positive cells and dentine resorption capacity in in vitro osteoclastogenesis assays. This correlated with fewer multinucleated osteoclast-like cells and more trabecular bone volume and number in 26-wk-old male IL-23p19-/- mice compared with control animals. Collectively, our data suggest that systemic IL-23 exposure induces the expansion of a myeloid lineage osteoclast precursor, and targeting IL-23 pathway may combat inflammation-driven bone destruction as observed in rheumatoid arthritis and other autoimmune arthritides.

Original languageEnglish (US)
Pages (from-to)951-959
Number of pages9
JournalJournal of Immunology
Volume187
Issue number2
DOIs
StatePublished - Jul 15 2011

ASJC Scopus subject areas

  • Immunology

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    Adamopoulos, I., Tessmer, M., Chao, C. C., Adda, S., Gorman, D., Petro, M., Chou, C. C., Pierce, R. H., Yao, W., Lane, N. E., Laface, D., & Bowman, E. P. (2011). IL-23 is critical for induction of arthritis, osteoclast formation, and maintenance of bone mass. Journal of Immunology, 187(2), 951-959. https://doi.org/10.4049/jimmunol.1003986