PMID- 36911207 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20230424 LR - 20230503 IS - 2452-199X (Electronic) IS - 2452-199X (Linking) VI - 26 DP - 2023 Aug TI - Macrophage-derived exosomes modulate wear particle-induced osteolysis via miR-3470b targeting TAB3/NF-kappaB signaling. PG - 181-193 LID - 10.1016/j.bioactmat.2023.02.028 [doi] AB - Aseptic prosthesis loosening (APL) is one of the most prevalent complications associated with arthroplasty. The main cause is the periprosthetic osteolysis induced by wear particles. However, the specific mechanisms of crosstalk between immune cells and osteoclasts/osteoblasts during osteolysis are unclear. In this study, we report the role and mechanism of macrophage-derived exosomes in wear particle-induced osteolysis. The results of exosomes up-taken experiments revealed that osteoblast and mature osteoclasts capture macrophage-derived exosomes (M-Exo). Next-generation sequencing and RT-qPCR on M-Exo revealed that exosomal microRNA miR-3470b was downregulated in wear particle-induced osteolysis. The results of analysis on Luciferase reporter assays/fluorescence in situ hybridization (FISH)/immunofluorescence (IF)/immunohistochemistry (IHC) and co-culture experiments demonstrated that wear particles induced osteoclast differentiation by increasing the expression of NFatc1 via M-Exo miR-3470b targeting TAB3/ NF-kappaB signaling. We also illustrate that engineered exosomes enriching miR-3470b facilitated to suppressed the osteolysis; the microenvironment enriching with miR-3470b could suppress wear particle-induced osteolysis via inhibition of TAB3/ NF-kappaB in vivo. In summary, our findings indicate that macrophage-derived exosomes transfer to osteoclasts to induce osteolysis in wear particle-induced APL. Engineering exosomes enriching with miR-3470b might be a novel strategy for the targeting treatment of bone resorption-related diseases. CI - (c) 2023 The Authors. FAU - Pan, Baiqi AU - Pan B AD - Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, China. AD - Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, China. FAU - Zhang, Ziji AU - Zhang Z AD - Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, China. AD - Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, China. FAU - Wu, Xiaoyu AU - Wu X AD - Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, China. AD - Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, China. FAU - Xian, Guoyan AU - Xian G AD - Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, China. AD - Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, China. AD - Universite de Paris, CNRS, INSERM, B3OA, Paris, France. FAU - Hu, Xuantao AU - Hu X AD - Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, China. AD - Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, China. FAU - Gu, Minghui AU - Gu M AD - Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, China. AD - Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, China. FAU - Zheng, Linli AU - Zheng L AD - Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, China. AD - Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, China. FAU - Li, Xiang AU - Li X AD - Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, China. AD - Department of Spine Surgery, The first affiliated hospital of Sun Yat-sen University, China. FAU - Long, Lingli AU - Long L AD - Research Center of Translational Medicine, The First Affiliated Hospital of Sun Yat-sen University, China. FAU - Chen, Weishen AU - Chen W AD - Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, China. AD - Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, China. FAU - Sheng, Puyi AU - Sheng P AD - Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, China. AD - Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, China. LA - eng PT - Journal Article DEP - 20230303 PL - China TA - Bioact Mater JT - Bioactive materials JID - 101685294 PMC - PMC9999169 OTO - NOTNLM OT - Aseptic prothesis loosening OT - Exosome OT - Inflammatory osteolysis OT - Macrophage OT - Non-coding RNA COIS- No potential conflict of interest was reported by the authors. EDAT- 2023/03/14 06:00 MHDA- 2023/03/14 06:01 PMCR- 2023/03/03 CRDT- 2023/03/13 04:22 PHST- 2022/12/06 00:00 [received] PHST- 2023/02/25 00:00 [revised] PHST- 2023/02/25 00:00 [accepted] PHST- 2023/03/14 06:00 [pubmed] PHST- 2023/03/14 06:01 [medline] PHST- 2023/03/13 04:22 [entrez] PHST- 2023/03/03 00:00 [pmc-release] AID - S2452-199X(23)00073-7 [pii] AID - 10.1016/j.bioactmat.2023.02.028 [doi] PST - epublish SO - Bioact Mater. 2023 Mar 3;26:181-193. doi: 10.1016/j.bioactmat.2023.02.028. eCollection 2023 Aug.