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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)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter H3k27me3, Bmal1 ; Kdm6b ; Circadian Rhythm ; Macrophage ; Osteogenesis; Macrophage Polarization; Histone; Demethylases
ISSN (print) / ISBN 1936-0851
e-ISSN 1936-086X
Zeitschrift ACS Nano
Quellenangaben Band: 17, Heft: 3, Seiten: 3153-3167 Artikelnummer: , Supplement: ,
Verlag American Chemical Society (ACS)
Verlagsort 1155 16th St, Nw, Washington, Dc 20036 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Regenerative Biology (IRBM)
Förderungen Center of Experimental Animals, Huazhong University of Science and Technology
National Science Foundation of China
Department of Science and Technology of Hubei Province