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The AP-1 transcription factor family is a central regulator of skin and bone homeostasis. We have previously shown that specific deletion of JunB/AP-1 in epidermis (JunBmice) results in skin inflammation,myeloproliferative disease, lupus-like disease and osteopenia. While upregulation of serum IL-6 and G-CSF are observed in this model, genetic deletion of these cytokines does not rescue osteopenia in JunB mice. Thus, we carried out a screen for other cytokines that are regulated by the loss of JunB in the epidermis. We have identified IL-17A as a cytokine expressed in JunB epidermis in vivo, and hypothesize that IL-17A leads to osteopenia in JunBmice. To test this,we carried out osteoblast and osteoclast differentiation assays in the presence of recombinant IL-17A or serum from JunB mice. Although there were no changes in osteoclast differentiation under these conditions, osteoblast differentiation, as visualized by Alizarin Red staining, was inhibited. Osteoblast differentiation markers were also downregulated in cultures in the presence of recombinant IL-17A or serum from JunB mice. To understand the mechanism by which IL-17A leads to inhibition of osteoblast differentiation, we stimulated osteoblasts with IL-17A in vitro, and observed upregulation in phospho-STAT3, phospho-NFkB andphospho-p38 levels. To determine if IL-17Aupregulation in the epidermis is sufficient to induce bone loss, we analyzed bones of mice ectopically expressing IL-17A in the epidermis. Thesemice displayed bone loss and had decreased levels of serumosteocalcin aswell as decreased osteoblast differentiationmarker expression in vivo. Therefore, thesedata suggest thatepidermal IL002D17A is able to inducebone loss through its action on osteoblast differentiation. These findings will likely be relevant for the treatment of patients with inflammatory diseases and skeletal involvement, such as psoriatic arthritis. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: None declared. doi:10.1016/j.bone.2012.02.078 OC08 Depletion of cytotoxic T cells at the time of bone injury enhances bone healing outcome K. Schmidt-Bleek⁎, I. Konnecke, A. Ellinghaus, H.-D. Volk, G.N. Duda, H. Schell Julius Wolff Institut, Charite-Universitatsmedizin Berlin, Berlin, Germany Institut for Medical Immunology, Charite-Universitatsmedizin Berlin |
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