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Haacke, N.* ; Wang, H.* ; Yan, S.* ; Barovic, M.* ; Li, X.* ; Nagai, K.* ; Botezatu, A.* ; Hatzioannou, A.* ; Gercken, B.* ; Trimaglio, G.* ; Shah, A.U.* ; Wang, J.* ; Ye, L.* ; Jaykar, M.T.* ; Rauner, M.* ; Wielockx, B.* ; Chung, K.J.* ; Netea, M.G.* ; Kalafati, L.* ; Hajishengallis, G.* ; Chavakis, T.

Innate immune training of osteoclastogenesis promotes inflammatory bone loss in mice.

Dev. Cell, DOI: 10.1016/j.devcel.2025.02.001 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
We previously demonstrated that long-term trained immunity (TRIM) involves adaptations that imprint innate immune memory in long-lived myelopoiesis precursors and their progeny, monocytes/macrophages and neutrophils, which thereby acquire enhanced responsiveness to future challenges. Here, we show that a distinct component of myeloid biology, osteoclastogenesis, can also undergo innate immune training. Indeed, β-glucan-induced TRIM was associated with an increased osteoclastogenesis bias in the bone marrow and an expansion of monocytes/osteoclast progenitors in the periphery, resulting in aggravated severity of experimental periodontitis and arthritis. In the setting of trained inflammatory osteoclastogenesis, we observed transcriptomic rewiring in synovial myeloid cells of arthritic mice, featuring prominent upregulation of the transcription factor melanogenesis-associated transcription factor (MITF). Adoptive transfer of splenic monocytes from β-glucan-trained mice to naive recipients exacerbated arthritis in the latter in a strictly MITF-dependent manner. Our findings establish trained osteoclastogenesis as a maladaptive component of TRIM and potentially provide therapeutic targets in inflammatory bone loss disorders.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Inflammatory Bone Loss ; Innate Immune Memory ; Monocytes ; Osteoclastogenesis ; Trained Immunity
ISSN (print) / ISBN 1534-5807
e-ISSN 1878-1551
Journal Developmental Cell
Publisher Elsevier
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Pancreatic Islet Research (IPI)