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Laser-mediated osteoblast ablation triggers a pro-osteogenic inflammatory response regulated by reactive oxygen species and glucocorticoid signaling in zebrafish

In zebrafish, transgenic labeling approaches, robust regenerative responses and excellent in vivo imaging conditions enable precise characterization of immune cell behavior in response to injury. Here, we monitored osteoblast-immune cell interactions in bone, a tissue which is particularly difficult to in vivo image in tetrapod species. Ablation of individual osteoblasts leads to recruitment of neutrophils and macrophages in varying numbers, depending on the extent of the initial insult, and initiates generation of cathepsin K+ osteoclasts from macrophages. Osteoblast ablation triggers the production of pro-inflammatory cytokines and reactive oxygen species, which are needed for successful macrophage recruitment. Excess glucocorticoid signaling as it occurs during the stress response inhibits macrophage recruitment, maximum speed and changes the macrophage phenotype. Although osteoblast loss is compensated for within a day by contribution of committed osteoblasts, macrophages continue to populate the region. Their presence is required for osteoblasts to fill the lesion site. Our model enables visualization of bone repair after microlesions at single-cell resolution and demonstrates a pro-osteogenic function of tissue-resident macrophages in non-mammalian vertebrates.

Identiferoai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89893
Date26 February 2024
CreatorsGeurtzen, Karina, López-Delgado, Alejandra Cristina, Duseja, Ankita, Kurzyukova, Anastasia, Knopf, Franziska
PublisherThe Company of Biologists
Source SetsHochschulschriftenserver (HSSS) der SLUB Dresden
LanguageEnglish
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text
Rightsinfo:eu-repo/semantics/openAccess
Relation1477-9129, 10.1242/dev.199803, info:eu-repo/grantAgreement/Deutsche Forschungsgemeinschaft/TRR 67: Funktionelle Biomaterialien zur Steuerung von Heilungsprozessen in Knochen- und Hautgewebe - vom Material zur Klinik/387653785//Die Rolle von Heparansulfat-Proteoglykanen bei der Knochenregeneration im Zebrafisch/B11*, info:eu-repo/grantAgreement/Deutsche Forschungsgemeinschaft/SPP 2084: µBONE: Kolonisierung und Interaktionen von Tumorzellen innerhalb des Knochenmilieus/359040200/

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