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Chronic skin inflammation leads to bone loss by IL-17-mediated inhibition of Wnt signaling in osteoblasts

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Chronic skin inflammation leads to bone loss by IL-17-mediated inhibition of Wnt signaling in osteoblasts. / Uluçkan, Özge; Jimenez, Maria; Karbach, Susanne; Jeschke, Anke; Graña, Osvaldo; Keller, Johannes; Busse, Björn; Croxford, Andrew L; Finzel, Stephanie; Koenders, Marije; van den Berg, Wim; Schinke, Thorsten; Amling, Michael; Waisman, Ari; Schett, Georg; Wagner, Erwin F.

In: SCI TRANSL MED, Vol. 8, No. 330, 16.03.2016, p. 330ra37.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Uluçkan, Ö, Jimenez, M, Karbach, S, Jeschke, A, Graña, O, Keller, J, Busse, B, Croxford, AL, Finzel, S, Koenders, M, van den Berg, W, Schinke, T, Amling, M, Waisman, A, Schett, G & Wagner, EF 2016, 'Chronic skin inflammation leads to bone loss by IL-17-mediated inhibition of Wnt signaling in osteoblasts', SCI TRANSL MED, vol. 8, no. 330, pp. 330ra37. https://doi.org/10.1126/scitranslmed.aad8996

APA

Uluçkan, Ö., Jimenez, M., Karbach, S., Jeschke, A., Graña, O., Keller, J., Busse, B., Croxford, A. L., Finzel, S., Koenders, M., van den Berg, W., Schinke, T., Amling, M., Waisman, A., Schett, G., & Wagner, E. F. (2016). Chronic skin inflammation leads to bone loss by IL-17-mediated inhibition of Wnt signaling in osteoblasts. SCI TRANSL MED, 8(330), 330ra37. https://doi.org/10.1126/scitranslmed.aad8996

Vancouver

Uluçkan Ö, Jimenez M, Karbach S, Jeschke A, Graña O, Keller J et al. Chronic skin inflammation leads to bone loss by IL-17-mediated inhibition of Wnt signaling in osteoblasts. SCI TRANSL MED. 2016 Mar 16;8(330):330ra37. https://doi.org/10.1126/scitranslmed.aad8996

Bibtex

@article{d93093a36b7743d7be38cfc6e4774a27,
title = "Chronic skin inflammation leads to bone loss by IL-17-mediated inhibition of Wnt signaling in osteoblasts",
abstract = "Inflammation has important roles in tissue regeneration, autoimmunity, and cancer. Different inflammatory stimuli can lead to bone loss by mechanisms that are not well understood. We show 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 correlated with increased serum IL-17A levels. Similarly, in two mouse models with chronic IL-17A-mediated skin inflammation,K14-IL17A(ind)andJunB(Δep), strong inhibition of bone formation was observed, 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 were able to express IL-17A, which acted systemically to inhibit osteoblast and osteocyte function by a mechanism involving Wnt signaling. IL-17A led to decreased Wnt signaling in vitro, and importantly, pharmacological blockade of IL-17A rescued Wnt target gene expression and bone formation in vivo. These data provide a mechanism where IL-17A affects bone formation by regulating Wnt signaling in osteoblasts and osteocytes. This study suggests that using IL-17A blocking agents in psoriasis could be beneficial against bone loss in these patients.",
keywords = "Animals, Bone Resorption, Cell Lineage, Chronic Disease, Epithelium, Female, Gene Expression Regulation, Humans, Inflammation, Interleukin-17, Male, Mice, Inbred C57BL, Middle Aged, Models, Biological, Osteoblasts, Osteocytes, Osteogenesis, Psoriasis, Skin, Wnt Signaling Pathway, Journal Article, Research Support, Non-U.S. Gov't",
author = "{\"O}zge Ulu{\c c}kan and Maria Jimenez and Susanne Karbach and Anke Jeschke and Osvaldo Gra{\~n}a and Johannes Keller and Bj{\"o}rn Busse and Croxford, {Andrew L} and Stephanie Finzel and Marije Koenders and {van den Berg}, Wim and Thorsten Schinke and Michael Amling and Ari Waisman and Georg Schett and Wagner, {Erwin F}",
note = "Copyright {\textcopyright} 2016, American Association for the Advancement of Science.",
year = "2016",
month = mar,
day = "16",
doi = "10.1126/scitranslmed.aad8996",
language = "English",
volume = "8",
pages = "330ra37",
journal = "SCI TRANSL MED",
issn = "1946-6234",
publisher = "AMER ASSOC ADVANCEMENT SCIENCE",
number = "330",

}

RIS

TY - JOUR

T1 - Chronic skin inflammation leads to bone loss by IL-17-mediated inhibition of Wnt signaling in osteoblasts

AU - Uluçkan, Özge

AU - Jimenez, Maria

AU - Karbach, Susanne

AU - Jeschke, Anke

AU - Graña, Osvaldo

AU - Keller, Johannes

AU - Busse, Björn

AU - Croxford, Andrew L

AU - Finzel, Stephanie

AU - Koenders, Marije

AU - van den Berg, Wim

AU - Schinke, Thorsten

AU - Amling, Michael

AU - Waisman, Ari

AU - Schett, Georg

AU - Wagner, Erwin F

N1 - Copyright © 2016, American Association for the Advancement of Science.

PY - 2016/3/16

Y1 - 2016/3/16

N2 - Inflammation has important roles in tissue regeneration, autoimmunity, and cancer. Different inflammatory stimuli can lead to bone loss by mechanisms that are not well understood. We show 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 correlated with increased serum IL-17A levels. Similarly, in two mouse models with chronic IL-17A-mediated skin inflammation,K14-IL17A(ind)andJunB(Δep), strong inhibition of bone formation was observed, 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 were able to express IL-17A, which acted systemically to inhibit osteoblast and osteocyte function by a mechanism involving Wnt signaling. IL-17A led to decreased Wnt signaling in vitro, and importantly, pharmacological blockade of IL-17A rescued Wnt target gene expression and bone formation in vivo. These data provide a mechanism where IL-17A affects bone formation by regulating Wnt signaling in osteoblasts and osteocytes. This study suggests that using IL-17A blocking agents in psoriasis could be beneficial against bone loss in these patients.

AB - Inflammation has important roles in tissue regeneration, autoimmunity, and cancer. Different inflammatory stimuli can lead to bone loss by mechanisms that are not well understood. We show 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 correlated with increased serum IL-17A levels. Similarly, in two mouse models with chronic IL-17A-mediated skin inflammation,K14-IL17A(ind)andJunB(Δep), strong inhibition of bone formation was observed, 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 were able to express IL-17A, which acted systemically to inhibit osteoblast and osteocyte function by a mechanism involving Wnt signaling. IL-17A led to decreased Wnt signaling in vitro, and importantly, pharmacological blockade of IL-17A rescued Wnt target gene expression and bone formation in vivo. These data provide a mechanism where IL-17A affects bone formation by regulating Wnt signaling in osteoblasts and osteocytes. This study suggests that using IL-17A blocking agents in psoriasis could be beneficial against bone loss in these patients.

KW - Animals

KW - Bone Resorption

KW - Cell Lineage

KW - Chronic Disease

KW - Epithelium

KW - Female

KW - Gene Expression Regulation

KW - Humans

KW - Inflammation

KW - Interleukin-17

KW - Male

KW - Mice, Inbred C57BL

KW - Middle Aged

KW - Models, Biological

KW - Osteoblasts

KW - Osteocytes

KW - Osteogenesis

KW - Psoriasis

KW - Skin

KW - Wnt Signaling Pathway

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1126/scitranslmed.aad8996

DO - 10.1126/scitranslmed.aad8996

M3 - SCORING: Journal article

C2 - 27089206

VL - 8

SP - 330ra37

JO - SCI TRANSL MED

JF - SCI TRANSL MED

SN - 1946-6234

IS - 330

ER -