PMID- 37220694 OWN - NLM STAT- MEDLINE DCOM- 20230619 LR - 20230619 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 120 DP - 2023 Jul TI - Oncostatin M regulates macrophages polarization in osseointegration via yes-associated protein. PG - 110348 LID - S1567-5769(23)00671-9 [pii] LID - 10.1016/j.intimp.2023.110348 [doi] AB - OBJECTIVES: Oncostatin M(OSM), secreted by monocytes and macrophages, has been noted to participate in bone homeostasis and macrophage polarization, which might be regulated by yes-associated protein (YAP). This study aimed to elucidate the influence and mechanisms of OSM-YAP on macrophages polarization in osseointegration. MATERIAL AND METHODS: In vitro, flow cytometry, real-time PCR, and Elisa were performed to evaluate inflammatory function in bone marrow-derived macrophages (BMDMs) with OSM, siOSMR, and YAP inhibitor verteporfin (VP). In vivo, macrophage-specific YAP-deficient mice were generated to investigate the role of OSM via YAP signaling in osseointegration. RESULTS: This study demonstrated that OSM could inhibit the M1 polarization, promote the M2 polarization, and induce the expression of osteogenic-related factors via VP. The conditional knock-out of YAP inhibited the osseointegration in mice, and promoted the inflammatory reaction around the implants, while OSM could restore the effect. CONCLUSIONS: Our results demonstrated that OSM might play an important role in the polarization of BMDMs, and bone formation around dental and femoral implants. This effect was closely conducted by Hippo-YAP pathway. CLINICAL SIGNIFICANCE: Understanding the role and mechanism of OSM in macrophage polarization around dental implants could improve comprehension of signal network of osseointegration, and it might offer a potential target of therapies to accelerate osseointegration and reduce inflammatory reactions. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Yuan, Ying AU - Yuan Y AD - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 400016, China. FAU - Zhang, Qin AU - Zhang Q AD - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Wu, Bingfeng AU - Wu B AD - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Huang, Tianyu AU - Huang T AD - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Gong, Ping AU - Gong P AD - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Xiang, Lin AU - Xiang L AD - State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address: dentistxiang@126.com. LA - eng PT - Journal Article DEP - 20230521 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 106956-32-5 (Oncostatin M) RN - 0 (YAP-Signaling Proteins) RN - 0 (Yap1 protein, mouse) RN - 0 (Osm protein, mouse) SB - IM MH - Animals MH - Mice MH - Inflammation/metabolism MH - Macrophages MH - Oncostatin M/metabolism MH - *Osseointegration MH - Signal Transduction MH - *YAP-Signaling Proteins OTO - NOTNLM OT - Bone biology OT - Bone remodeling/regeneration OT - Cell signaling OT - Dental implant(s) OT - Immunity COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/05/23 19:09 MHDA- 2023/06/16 06:42 CRDT- 2023/05/23 18:00 PHST- 2023/03/06 00:00 [received] PHST- 2023/05/04 00:00 [revised] PHST- 2023/05/12 00:00 [accepted] PHST- 2023/06/16 06:42 [medline] PHST- 2023/05/23 19:09 [pubmed] PHST- 2023/05/23 18:00 [entrez] AID - S1567-5769(23)00671-9 [pii] AID - 10.1016/j.intimp.2023.110348 [doi] PST - ppublish SO - Int Immunopharmacol. 2023 Jul;120:110348. doi: 10.1016/j.intimp.2023.110348. Epub 2023 May 21.