PMID- 37533592 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230804 IS - 1687-966X (Print) IS - 1687-9678 (Electronic) VI - 2023 DP - 2023 TI - The m(6)A Reader YTHDF1 Accelerates the Osteogenesis of Bone Marrow Mesenchymal Stem Cells Partly via Activation of the Autophagy Signaling Pathway. PG - 5563568 LID - 10.1155/2023/5563568 [doi] LID - 5563568 AB - N6-methyladenosine (m(6)A) mRNA methylation has emerged as an important player in many biological processes by regulating gene expression. As a crucial reader, YTHDF1 usually improves the translation efficiency of its target mRNAs. However, its roles in bone marrow mesenchymal stem cells (BMSCs) osteogenesis remain largely unknown. Here, we reported that YTHDF1, an m(6)A reader, is highly expressed during osteogenic differentiation of BMSCs. Upregulation of YTHDF1 increased osteogenic differentiation and proliferation capacity of BMSCs. Accordingly, downregulation of YTHDF1 inhibited osteogenic differentiation and proliferation capacity. Possible underlying mechanisms were explored, and analysis revealed that YTHDF1 could affect autophagy levels, thus regulating osteogenesis of BMSCs. In an in vivo study, we found that upregulation of YTHDF1 accelerates fracture healing with elevated bone volume fraction and trabecular thickness. Taken together, our study revealed that m(6)A reader YTHDF1 accelerates osteogenic differentiation of BMSCs partly via the autophagy signaling pathway. These findings reveal a previously unrecognized mechanism involved in the regulation of BMSCs osteogenesis, providing new ideas and target sites for the treatment of fracture. CI - Copyright (c) 2023 Xiang Gao et al. FAU - Gao, Xiang AU - Gao X AUID- ORCID: 0000-0002-4557-8231 AD - Department of Orthopedic Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. AD - Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, China. AD - Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, Zhejiang, China. FAU - Wang, Jian AU - Wang J AUID- ORCID: 0009-0005-2983-0993 AD - Department of Orthopedic Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. AD - Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, China. AD - Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, Zhejiang, China. FAU - Wang, Yibo AU - Wang Y AUID- ORCID: 0000-0002-2941-7841 AD - Department of Orthopedic Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. AD - Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, China. AD - Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, Zhejiang, China. FAU - Li, Weixu AU - Li W AUID- ORCID: 0000-0002-6742-3230 AD - Department of Orthopedic Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. AD - Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, China. AD - Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, Zhejiang, China. FAU - Pan, Zhijun AU - Pan Z AUID- ORCID: 0000-0002-4618-5990 AD - Department of Orthopedic Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. AD - Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, China. AD - Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, Zhejiang, China. LA - eng PT - Journal Article DEP - 20230725 PL - United States TA - Stem Cells Int JT - Stem cells international JID - 101535822 PMC - PMC10393526 COIS- The authors declare that the research was conducted in the absence of commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/08/03 06:43 MHDA- 2023/08/03 06:44 PMCR- 2023/07/25 CRDT- 2023/08/03 03:53 PHST- 2023/03/07 00:00 [received] PHST- 2023/06/04 00:00 [revised] PHST- 2023/06/26 00:00 [accepted] PHST- 2023/08/03 06:44 [medline] PHST- 2023/08/03 06:43 [pubmed] PHST- 2023/08/03 03:53 [entrez] PHST- 2023/07/25 00:00 [pmc-release] AID - 10.1155/2023/5563568 [doi] PST - epublish SO - Stem Cells Int. 2023 Jul 25;2023:5563568. doi: 10.1155/2023/5563568. eCollection 2023.