Eosinophils preserve bone homeostasis by inhibiting excessive osteoclast formation and activity via eosinophil peroxidase

Darja Andreev (), Katerina Kachler, Mengdan Liu, Zhu Chen, Brenda Krishnacoumar, Mark Ringer, Silke Frey, Gerhard Krönke, David Voehringer, Georg Schett and Aline Bozec ()
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Darja Andreev: Friedrich-Alexander-University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Katerina Kachler: Friedrich-Alexander-University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Mengdan Liu: Friedrich-Alexander-University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Zhu Chen: Friedrich-Alexander-University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Brenda Krishnacoumar: Friedrich-Alexander-University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Mark Ringer: Friedrich-Alexander-University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Silke Frey: Friedrich-Alexander-University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Gerhard Krönke: Friedrich-Alexander-University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
David Voehringer: FAU Erlangen-Nürnberg and Universitätsklinikum Erlangen
Georg Schett: Friedrich-Alexander-University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Aline Bozec: Friedrich-Alexander-University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: Abstract Eosinophils are involved in tissue homeostasis. Herein, we unveiled eosinophils as important regulators of bone homeostasis. Eosinophils are localized in proximity to bone-resorbing osteoclasts in the bone marrow. The absence of eosinophils in ΔdblGATA mice results in lower bone mass under steady-state conditions and amplified bone loss upon sex hormone deprivation and inflammatory arthritis. Conversely, increased numbers of eosinophils in IL-5 transgenic mice enhance bone mass under steady-state conditions and protect from hormone- and inflammation- mediated bone loss. Eosinophils strongly inhibit the differentiation and demineralization activity of osteoclasts and lead to profound changes in the transcriptional profile of osteoclasts. This osteoclast-suppressive effect of eosinophils is based on the release of eosinophil peroxidase causing impaired reactive oxygen species and mitogen-activated protein kinase induction in osteoclast precursors. In humans, the number and the activity of eosinophils correlates with bone mass in healthy participants and rheumatoid arthritis patients. Taken together, experimental and human data indicate a regulatory function of eosinophils on bone.

Date: 2024
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DOI: 10.1038/s41467-024-45261-8

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