IL-23 Is Critical for Induction of Arthritis, Osteoclast Formation, and Maintenance of Bone Mass

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. The Journal of Immunology, 2011, 187: 951–959.

In Situ Analysis of Interleukin–23– and Interleukin‐12–Positive Cells in the Spine of Patients With Ankylosing Spondylitis

“…In the latter model IL-23 was necessary for induction of lung fibrosis by transforming growth factor ␤. There is evidence that IL-23 might have a different effect under inflammatory conditions versus noninflammatory conditions: it can mediate bonedestructive processes (32,33) and is found within inflammatory lesions in the gut mucosa of patients with Crohn's disease (34), but also induces increased bone mass under noninflammatory conditions (35). We and others have hypothesized that new bone formation starts from fibrous tissue and that the development of fibrous tissue is crucial in AS (4,13,14).…”

Editorial: Animal Models of Spondyloarthritis: Do They Faithfully Mirror Human Disease?

“…The use of minicircle DNA technology to express IL-23 in the hepatocytes of B10.RIII mice resulted in a destructive polyarthritis that was found to be independent of CD4ϩ T cells (15). Recently, Sherlock et al (16) reported that the resulting in vivo expression of IL-23 was sufficient to induce enthesitis and entheseal new bone formation in the initial complete absence of synovitis.…”

The immune system and postmenopausal osteoporosis

“…However, in contrast to IL-17-deficient mice, IL-23 knockout mice are completely protected from bone and joint destruction in the collagen-induced arthritis model, indicating that the IL-23-induced bone loss may not be entirely mediated by IL-17, and raising the question whether IL-23 can directly stimulate OCs. Recent work supports this hypothesis suggesting that IL-23 promotes OCs formation (Adamopoulos et al, 2011;Chen et al, 2008;Hu et al, 2013;Yago et al, 2007). Other recent in vivo studies suggest that IL-23 inhibits OC formation via T cells (Quinn et al, 2008).…”