PMID- 36715347 OWN - NLM STAT- MEDLINE DCOM- 20230216 LR - 20240131 IS - 1936-086X (Electronic) IS - 1936-0851 (Print) IS - 1936-0851 (Linking) VI - 17 IP - 3 DP - 2023 Feb 14 TI - Dual-Targeted Nanodiscs Revealing the Cross-Talk between Osteogenic Differentiation of Mesenchymal Stem Cells and Macrophages. PG - 3153-3167 LID - 10.1021/acsnano.2c12440 [doi] AB - 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-kappaB 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. FAU - Chen, Lang AU - Chen L AD - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. AD - Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China. FAU - Yu, Chenyan AU - Yu C AD - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. AD - Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China. FAU - Xu, Wanting AU - Xu W AD - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. AD - School of Pharmaceutical Sciences, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518100, China. FAU - Xiong, Yuan AU - Xiong Y AD - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. AD - Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China. FAU - Cheng, Peng AU - Cheng P AD - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. AD - Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China. FAU - Lin, Ze AU - Lin Z AD - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. AD - Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China. FAU - Zhang, Zhenhe AU - Zhang Z AD - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. AD - Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China. FAU - Knoedler, Leonard AU - Knoedler L AD - Department of Plastic, Hand and Reconstructive Surgery, University Hospital Regensburg, Regensburg 93053, Germany. AD - Leibniz Institute of Immunotherapy, University of Regensburg, Regensburg 93053, Germany. FAU - Panayi, Adriana C AU - Panayi AC AD - Department of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02152, United States. AD - Department of Hand, Plastic and Reconstructive Surgery, Microsurgery, Burn Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwig-Guttmann-Strasse 13, Ludwigshafen/Rhine 67071, Germany. FAU - Knoedler, Samuel AU - Knoedler S AD - Department of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02152, United States. AD - Institute of Regenerative Biology and Medicine, Helmholtz Zentrum Munchen, Max-Lebsche-Platz 31, Munich 81377, Germany. FAU - Wang, Junqing AU - Wang J AUID- ORCID: 0000-0002-9091-9891 AD - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. AD - School of Pharmaceutical Sciences, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518100, China. FAU - Mi, Bobin AU - Mi B AD - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. AD - Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China. FAU - Liu, Guohui AU - Liu G AUID- ORCID: 0000-0002-2013-1396 AD - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. AD - Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230130 PL - United States TA - ACS Nano JT - ACS nano JID - 101313589 RN - 0 (ARNTL Transcription Factors) RN - K3Z4F929H6 (Lysine) SB - IM MH - *Osteogenesis MH - ARNTL Transcription Factors/metabolism MH - Lysine MH - Cell Differentiation/genetics MH - *Mesenchymal Stem Cells MH - Macrophages/metabolism MH - Cells, Cultured PMC - PMC9933878 OTO - NOTNLM OT - H3K27me3, BMAL1 OT - KDM6B OT - circadian rhythm OT - macrophage OT - osteogenesis COIS- The authors declare no competing financial interest. EDAT- 2023/01/31 06:00 MHDA- 2023/02/17 06:00 PMCR- 2024/01/30 CRDT- 2023/01/30 07:34 PHST- 2023/01/31 06:00 [pubmed] PHST- 2023/02/17 06:00 [medline] PHST- 2023/01/30 07:34 [entrez] PHST- 2024/01/30 00:00 [pmc-release] AID - 10.1021/acsnano.2c12440 [doi] PST - ppublish SO - ACS Nano. 2023 Feb 14;17(3):3153-3167. doi: 10.1021/acsnano.2c12440. Epub 2023 Jan 30.