PMID- 36610229 OWN - NLM STAT- MEDLINE DCOM- 20240123 LR - 20240123 IS - 1532-3072 (Electronic) IS - 0040-8166 (Linking) VI - 81 DP - 2023 Apr TI - MicroRNA-211-5p in extracellular vesicles derived from BMSCs facilitates the repair of rat frozen shoulder via regulating KDM2B/LACC1 axis. PG - 102006 LID - S0040-8166(22)00278-6 [pii] LID - 10.1016/j.tice.2022.102006 [doi] AB - OBJECTIVE: This study aims to explore the mechanism of miR-211-5p in extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (BMSCs) in improving frozen shoulder (FS) in rat models. METHODS: Rat BMSCs and EVs derived from rat BMSCs were isolated, identified, and then injected into rats to assess the expression of TGF-beta, MMP1, MMP3, MMP12, GAP43, and PGP9.5 in shoulder capsule tissues. The range of motion of bilateral glenohumeral joints was assessed and pathological changes of shoulder capsule tissues were observed after hematoxylin-eosin staining. The binding sites of miR-211-5p to KDM2B and LACC1 to H3K4me3 were measured. FS rat models with LACC1 highly expressed were established to assess the motion of bilateral glenohumeral joints and expression of arthritis related factors in rats. RESULTS: EVs were successfully extracted from BMSCs. Injection of BMSCs-EVs could improve the activity of bilateral glenohumeral joints and the pathological condition of joint capsule in rats. Elevated expression of miR-211-5p was found in rats injected with BMSCs-EVs. Dual luciferase assay showed that miR-211-5p had a binding site with KDM2B. ChIP, qRT-PCR, and western blot experiments showed BMSCs-EVs injection resulted in elevated enrichment of LACC1 promoter in shoulder capsule tissues of FS rats, and decreased mRNA and protein expression of KDM2B and increased H3K4me3 methylation. Overexpression of LACC1 could also improve the pathological condition of joint capsule tissue. CONCLUSION: miR-211-5p in EVs derived from BMSCs increased H3K4me3 methylation in shoulder capsule tissue of rats by binding KDM2B, resulting in up-regulated transcription level of LACC1 and improving FS. AVAILABILITY OF DATA AND MATERIALS: The datasets used or analyzed during the current study are available from the corresponding author on reasonable request. CI - Copyright (c) 2023 Elsevier Ltd. All rights reserved. FAU - Mao, Xiaodong AU - Mao X AD - Department of Orthopedics & Traumatology, Department of Joint Surgery, Changsha Hospital of Traditional Chinese Medicine, Changsha Eighth Hospital, Changsha, Hunan 410008, PR China. FAU - Li, Zhi AU - Li Z AD - Department of Orthopedics & Traumatology, Department of Joint Surgery, Changsha Hospital of Traditional Chinese Medicine, Changsha Eighth Hospital, Changsha, Hunan 410008, PR China. FAU - Gu, Shaofang AU - Gu S AD - Department of Orthopedics & Traumatology, Department of Joint Surgery, Changsha Hospital of Traditional Chinese Medicine, Changsha Eighth Hospital, Changsha, Hunan 410008, PR China. FAU - Song, Wei AU - Song W AD - Department of Orthopedics & Traumatology, Department of Joint Surgery, Changsha Hospital of Traditional Chinese Medicine, Changsha Eighth Hospital, Changsha, Hunan 410008, PR China. FAU - Zhang, Mimi AU - Zhang M AD - Department of Orthopedics & Traumatology, Department of Joint Surgery, Changsha Hospital of Traditional Chinese Medicine, Changsha Eighth Hospital, Changsha, Hunan 410008, PR China. FAU - Tan, Xiao AU - Tan X AD - Department of Orthopedics & Traumatology, Department of Joint Surgery, Changsha Hospital of Traditional Chinese Medicine, Changsha Eighth Hospital, Changsha, Hunan 410008, PR China. FAU - Mao, Ziqing AU - Mao Z AD - Department of Orthopedics & Traumatology, Department of Joint Surgery, Changsha Hospital of Traditional Chinese Medicine, Changsha Eighth Hospital, Changsha, Hunan 410008, PR China. Electronic address: 329512897@qq.com. LA - eng PT - Journal Article DEP - 20221222 PL - Scotland TA - Tissue Cell JT - Tissue & cell JID - 0214745 RN - 0 (F-Box Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - EC 1.14.11.- (Jumonji Domain-Containing Histone Demethylases) RN - 0 (MicroRNAs) RN - 0 (MIRN211 microRNA, rat) RN - 0 (Lacc1 protein, rat) RN - 0 (Kdm2b protein, rat) SB - IM MH - Animals MH - Rats MH - *Bursitis/genetics/metabolism MH - *Extracellular Vesicles/genetics/metabolism MH - F-Box Proteins/genetics/metabolism MH - Intracellular Signaling Peptides and Proteins/genetics/metabolism MH - Jumonji Domain-Containing Histone Demethylases/genetics/metabolism MH - *Mesenchymal Stem Cells/metabolism MH - *MicroRNAs/genetics/metabolism OTO - NOTNLM OT - Bone marrow mesenchymal stem cells OT - Frozen shoulder OT - KDM2B OT - LACC1 OT - MicroRNA-211-5p COIS- Conflict of interests The authors declare there is no conflict of interests. EDAT- 2023/01/08 06:00 MHDA- 2023/03/21 06:00 CRDT- 2023/01/07 18:10 PHST- 2022/07/06 00:00 [received] PHST- 2022/12/21 00:00 [revised] PHST- 2022/12/21 00:00 [accepted] PHST- 2023/01/08 06:00 [pubmed] PHST- 2023/03/21 06:00 [medline] PHST- 2023/01/07 18:10 [entrez] AID - S0040-8166(22)00278-6 [pii] AID - 10.1016/j.tice.2022.102006 [doi] PST - ppublish SO - Tissue Cell. 2023 Apr;81:102006. doi: 10.1016/j.tice.2022.102006. Epub 2022 Dec 22.