Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
The interleukin (IL)-23/IL-17A immune pathway is critical for the development of autoimmune arthritis. Systemic exposure of IL-23 induced chronic arthritis, increased osteoclast differentiation and systemic bone loss in mice. However, the role of IL-23 on normal and pathologic bone remodeling is not fully elucidated. Here we examined the role of IL-23R signaling on bone remodeling in steady state and on bone damage during a T cell-mediated inflammatory arthritis using wild type (WT) and IL-23RKO mice.
Femurs of naïve WT and IL-23RKO mice were used for MicroCT analysis of the bone and a three-point bending test for bone strength. Bone marrow cells (BM) were cultured towards osteoclasts with MCSF, RANKL and +/- IL-17 and assessed for osteoclast-like cells using tartrate-resistant acid phosphatase (TRAP) staining and bone resorption assay.
For antigen-induced arthritis (AIA), WT and IL-23RGFP+ /GFP+ (IL-23RKO) mice were immunized with methylated bovine serum albumin (mBSA) supplemented in Complete Freund’s Adjuvant. After 7 days mice were injected in the knee joints with mBSA. Mice were macroscopically scored at given time points and knees were used for histological analysis of joint inflammation and bone erosion.
MicroCT data revealed a low bone mass phenotype in naïve IL-23RKO mice compared to WT mice, with lower trabecular bone volume fraction, thickness and number as well as lower cortical volume and thickness. Three-point bending data show significantly reduced maximum force in IL-23RKO femurs. However, IL-17 stimulation of both WT and IL-23RKO BM cells increased osteoclast bone resorption activity in vitro.
In contrast, histological analysis revealed significantly less inflammation-mediated bone damage in knees of IL-23RKO versus WT mice during AIA. This was accompanied with significantly less severe joint inflammation, although the onset of arthritis was not prevented in IL-23RKO mice.
IL-23R signaling is important for the maintenance of bone mass under steady state conditions. However, although the effect of IL-17A on bone resorption is independent of IL-23R signaling, T cell driven inflammatory bone erosion during arthritis is IL-23R signaling dependent.
To cite this abstract in AMA style:Razawy W, Koedam M, Asmawidjaja P, Otten-Mus AM, van der Eerden B, Lubberts E. A Dual Role for IL-23 Receptor Signaling in Normal Bone Remodeling Versus Inflammation-Mediated Bone Damage during Arthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). http://acrabstracts.org/abstract/a-dual-role-for-il-23-receptor-signaling-in-normal-bone-remodeling-versus-inflammation-mediated-bone-damage-during-arthritis/. Accessed January 20, 2018.
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