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Bone Abstracts (2016) 5 P147 | DOI: 10.1530/boneabs.5.P147

1CNIO, Madrid, Spain; 2University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 3University of Mainz, Mainz, Germany; 4University of Erlangen-Nuremberg, Erlangen, Germany.

Inflammatory stimuli can lead to bone loss by mechanisms that are not well understood. We recently showed that skin inflammation induces bone loss in mice and humans. In psoriasis, one of the prototypic IL-17A-mediated inflammatory human skin diseases, low bone formation and bone loss correlates with increased serum IL-17A levels. Similarly, in two mouse models with chronic IL-17A-mediated skin inflammation, K14-IL17Aind and JunBΔep, strong inhibition of bone formation occurs, different from classical inflammatory bone loss where osteoclast activation leads to bone degradation. We show that under inflammatory conditions skin resident cells, such as keratinocytes, γδ T cells and innate lymphoid cells express IL-17A, which act systemically to inhibit osteoblast and osteocyte function by a mechanism involving Wnt signaling. IL-17A leads to decreased Wnt signaling in vitro and, importantly pharmacological blockade of IL-17A rescues Wnt target gene expression and bone formation in vivo.

To determine the contribution of T-cell-derived IL-17A to skin inflammation and bone loss, we crossed the JunBΔep mice to Rag1−/− (DKO) mice. Interestingly, we observed exacerbated skin inflammation and earlier onset of bone loss. IL-17A expression was highly abundant in the skin of the DKO mice with increased infiltration of innate immune cells, such as neutrophils and mast cells. These mice were also prone to S.aureus infections. Antibiotic treatments reduced skin inflammation and bone loss. We are currently investigating the IL-17A producing cells in the skin in the absence of mature B and T cells, and their possible mobilization to the bone by using the IL-17A-GFP reporter mouse. Metagenomic sequencing of the skin microbiota, as well as germ-free housing of these mice, will allow us to determine the role of different commensal bacteria populations in skin inflammation and bone loss. This study adds the dimension of the role of microbiota to the current understanding of osteoimmunology.

Volume 5

43rd Annual European Calcified Tissue Society Congress

Rome, Italy
14 May 2016 - 17 May 2016

European Calcified Tissue Society 

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