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Chen, L.* ; Yu, C.* ; Xu, W.* ; Xiong, Y.* ; Cheng, P.* ; Lin, Z.* ; Zhang, Z.* ; Knoedler, L.* ; Panayi, A.C.* ; Knoedler, S. ; Wang, J.* ; Mi, B.* ; Liu, G.*

Dual-targeted nanodiscs revealing the cross-talk between osteogenic differentiation of mesenchymal stem cells and macrophages.

ACS Nano 17, 3153-3167 (2023)
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Ongoing research has highlighted the significance of the cross-play of macrophages and mesenchymal stem cells (MSCs). Lysine-specific demethylase 6B (KDM6B) has been shown to control osteogenic differentiation of MSCs by depleting trimethylated histone 3 lysine 27 (H3K27me3). However, to date, the role of KDM6B in bone marrow-derived macrophages (BMDMs) remains controversial. Here, a chromatin immunoprecipitation assay (ChIP) proved that KDM6B derived from osteogenic-induced BMSCs could bind to the promoter region of BMDMs' brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 (BMAL1) gene in a coculture system and activate BMAL1. Transcriptome sequencing and experiments in vitro showed that the overexpression of BMAL1 in BMDM could inhibit the TLR2/NF-κB signaling pathway, reduce pyroptosis, and decrease the M1/M2 ratio, thereby promoting osteogenic differentiation of BMSCs. Furthermore, bone and macrophage dual-targeted GSK-J4 (KDM6B inhibitor)-loaded nanodiscs were synthesized via binding SDSSD-apoA-1 peptide analogs (APA) peptide, which indirectly proved the critical role of KDM6B in osteogenesis in vivo. Overall, we demonstrated that KDM6B serves as a positive circulation trigger during osteogenic differentiation by decreasing the ratio of M1/M2 both in vitro and in vivo. Collectively, these results provide insight into basic research in the field of osteoporosis and bone repair.
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Publication type Article: Journal article
Document type Scientific Article
Keywords H3k27me3, Bmal1 ; Kdm6b ; Circadian Rhythm ; Macrophage ; Osteogenesis; Macrophage Polarization; Histone; Demethylases
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 1936-0851
e-ISSN 1936-086X
Journal ACS Nano
Quellenangaben Volume: 17, Issue: 3, Pages: 3153-3167 Article Number: , Supplement: ,
Publisher American Chemical Society (ACS)
Publishing Place 1155 16th St, Nw, Washington, Dc 20036 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Regenerative Biology and Medicine (IRBM)
POF-Topic(s) 30202 - Environmental Health
Research field(s) Lung Research
PSP Element(s) G-509400-001
Grants Center of Experimental Animals, Huazhong University of Science and Technology
National Science Foundation of China
Department of Science and Technology of Hubei Province
DOI 10.1021/acsnano.2c12440
WOS ID 000926704800001
Scopus ID 85147263076
PubMed ID 36715347
Erfassungsdatum 2023-02-01
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