Interleukin-23 Regulates Inflammatory Osteoclastogenesis Via Activation of CLEC5A(+) Osteoclast Precursors

Overview

Journal Arthritis Rheumatol

Publisher Wiley

Specialty Rheumatology

Date 2023 Feb 14

PMID 36787107

Authors

Hiroki Furuya

Cuong Thach Nguyen

Ran Gu

Shie-Liang Hsieh

Emanual Maverakis

Iannis E Adamopoulos

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate the role of interleukin-23 (IL-23) in pathologic bone remodeling in inflammatory arthritis.

Methods: In this study we investigated the role of IL-23 in osteoclast differentiation and activation using in vivo gene transfer techniques in wild-type and myeloid DNAX-activation protein 12-associating lectin-1 (MDL-1)-deficient mice, and by performing in vitro and in vivo osteoclastogenesis assays using spectral flow cytometry, micro-computed tomography analysis, Western blotting, and immunoprecipitation.

Results: Herein, we show that IL-23 induces the expansion of a myeloid osteoclast precursor population and supports osteoclastogenesis and bone resorption in inflammatory arthritis. Genetic ablation of C-type lectin domain family member 5A, also known as MDL-1, prevents the induction of osteoclast precursors by IL-23 that is associated with bone destruction, as commonly observed in inflammatory arthritis. Moreover, osteoclasts derived from the bone marrow of MDL-1-deficient mice showed impaired osteoclastogenesis, and MDL-1 mice had increased bone mineral density.

Conclusion: Our data show that IL-23 signaling regulates the availability of osteoclast precursors in inflammatory arthritis that could be effectively targeted for the treatment of inflammatory bone loss in inflammatory arthritis.

Citing Articles

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