The interleukin (IL)−23/IL-17A immune pathway is critical for the development of autoimmune arthritis. Moreover, 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 remodelling is not fully elucidated.Background
We studied the role of IL-23R signalling on normal bone phenotype and bone damage during a T cell-mediated inflammatory arthritis in vivo and osteoclast differentiation and activity in vitro.Materials and methods
For antigen-induced arthritis (AIA), WT and IL-23RGFP+/GFP+ (IL-23R/-) mice were immunised with methylated bovine serum albumin (mBSA) in supplemented 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.Materials and methods
Naïve WT and IL-23R/- bone marrow cells (BM) were cultured towards osteoclasts with MCSF, RANKL and +/- IL-23 and assessed for tartrate-resistant acid phosphatase (TRAP) staining, qPCRs and bone resorption. Femurs were used for MicroCT analysis and three-point bending test.Results
During AIA the onset of disease was not prevented in IL-23R-/- mice. However, the progression of arthritis was diminished, resulting in significantly less disease. Histological analysis revealed significantly less inflammation-mediated bone damage in knees of IL-23R/- versus WT mice.Results
In vitro, IL-23 had no direct effect on the number of TRAP+ cells, but increased bone resorption by osteoclasts. Interestingly, microCT data revealed a low bone mass phenotype in IL-23R-/- mice, with lower trabecular bone volume fraction, thickness and number as well as lower cortical volume and thickness. Preliminary three-point bending data show significantly reduced maximum force in IL-23RKO femurs.Conclusions
In vitro, IL-23 is involved in the activation of osteoclasts. Whereas T cell-driven inflammatory bone erosion is IL-23R signalling mediated, during normal bone remodelling IL-23R signalling is important for the maintenance of bone mass.