Trained innate immunity modulates osteoblast and osteoclast differentiation.

Autor: Rahmani NR; Department of Orthopedics, University Medical Center Utrecht, Utrecht, the Netherlands. n.r.rahmani@umcutrecht.nl.; Regenerative Medicine Center Utrecht, Utrecht University, Utrecht, the Netherlands. n.r.rahmani@umcutrecht.nl., Belluomo R; Regenerative Medicine Center Utrecht, Utrecht University, Utrecht, the Netherlands., Kruyt MC; Department of Orthopedics, University Medical Center Utrecht, Utrecht, the Netherlands.; Department of Developmental Biomedical Engineering, Twente University, Enschede, the Netherlands., Gawlitta D; Regenerative Medicine Center Utrecht, Utrecht University, Utrecht, the Netherlands.; Department of Oral and Maxillofacial Surgery, Prosthodontics and Special Dental Care, University Medical Center Utrecht, Utrecht, the Netherlands., Joosten LAB; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.; Department of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania., Weinans H; Department of Orthopedics, University Medical Center Utrecht, Utrecht, the Netherlands.; Department of Biomechanical Engineering, Technical University Delft, Delft, the Netherlands., Croes M; Department of Orthopedics, University Medical Center Utrecht, Utrecht, the Netherlands.
Jazyk: angličtina
Zdroj: Stem cell reviews and reports [Stem Cell Rev Rep] 2024 May; Vol. 20 (4), pp. 1121-1134. Date of Electronic Publication: 2024 Mar 13.
DOI: 10.1007/s12015-024-10711-9
Abstrakt: Macrophages are key regulators in bone repair and regeneration. Recent studies have shown that long-term epigenetic changes and metabolic shifts occur during specific immune training of macrophages that affect their functional state, resulting in heightened (trained) or reduced (tolerant) responses upon exposure to a second stimulus. This is known as innate immune memory. Here, we study the impact of macrophages' memory trait on osteoblast differentiation of human mesenchymal stromal cells (hMSCs) and osteoclast differentiation. An in vitro trained immunity protocol of monocyte-derived macrophages was employed using inactivated Candida albicans and Bacillus Calmette-Guérin (BCG) to induce a 'trained' state and Pam3CSK4 (PAM) and Lipopolysaccharides (LPS) to induce a 'tolerance' state. Macrophages were subsequently cocultured with hMSCs undergoing osteogenic differentiation during either resting (unstimulated) or inflammatory conditions (restimulated with LPS). Alkaline phosphatase activity, mineralization, and cytokine levels (TNF, IL-6, oncostatin M and SDF-1α) were measured. In addition, macrophages underwent osteoclast differentiation. Our findings show that trained and tolerized macrophages induced opposing results. Under resting conditions, BCG-trained macrophages enhanced ALP levels (threefold), while under inflammatory conditions this was found in the LPS-tolerized macrophages (fourfold). Coculture of hMSCs with trained macrophages showed mineralization while tolerized macrophages inhibited the process under both resting and inflammatory conditions. While osteoclast differentiation was not affected in trained-macrophages, this ability was significantly loss in tolerized ones. This study further confirms the intricate cross talk between immune cells and bone cells, highlighting the need to consider this interaction in the development of personalized approaches for bone regenerative medicine.
(© 2024. The Author(s).)
Databáze: MEDLINE
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