Akkermansia muciniphila promotes type H vessel formation and bone fracture healing by reducing gut permeability and inflammation.

Autor:	Liu JH; Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China., Yue T; Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China., Luo ZW; Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China., Cao J; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China., Yan ZQ; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.; Department of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China., Jin L; Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China., Wan TF; Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China., Shuai CJ; State Key Laboratory of High Performance Complex Manufacturing, College of Mechanical and Electrical Engineering, Central South University, Changsha, Hunan 410008, China., Wang ZG; Department of Orthopedics, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China., Zhou Y; Department of Orthopedics, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China huixie@csu.edu.cn xuran@csu.edu.cn zhouyong1028@sina.com., Xu R; Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410008, China huixie@csu.edu.cn xuran@csu.edu.cn zhouyong1028@sina.com., Xie H; Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China huixie@csu.edu.cn xuran@csu.edu.cn zhouyong1028@sina.com.; Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.; Hunan Key Laboratory of Organ Injury, Aging and Regenerative Medicine, Changsha, Hunan 410008 China.; Hunan Key Laboratory of Bone Joint Degeneration and Injury, Changsha, Hunan 410008, China.; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Jazyk:	angličtina
Zdroj:	Disease models & mechanisms [Dis Model Mech] 2020 Dec 01; Vol. 13 (11). Date of Electronic Publication: 2020 Dec 01.
DOI:	10.1242/dmm.043620
Abstrakt:	Improving revascularization is one of the major measures in fracture treatment. Moderate local inflammation triggers angiogenesis, whereas systemic inflammation hampers angiogenesis. Previous studies showed that Akkermansia muciniphila , a gut probiotic, ameliorates systemic inflammation by tightening the intestinal barrier. In this study, fractured mice intragastrically administrated with A. muciniphila were found to display better fracture healing than mice treated with vehicle. Notably, more preosteclasts positive for platelet-derived growth factor-BB (PDGF-BB) were induced by A. muciniphila at 2 weeks post fracture, coinciding with increased formation of type H vessels, a specific vessel subtype that couples angiogenesis and osteogenesis, and can be stimulated by PDGF-BB. Moreover, A. muciniphila treatment significantly reduced gut permeability and inflammation at the early stage. Dextran sulfate sodium (DSS) was used to disrupt the gut barrier to determine its role in fracture healing and whether A. muciniphila still can stimulate bone fracture healing. As expected, A. muciniphila evidently improved gut barrier, reduced inflammation and restored the impaired bone healing and angiogenesis in DSS-treated mice. Our results suggest that A. muciniphila reduces intestinal permeability and alleviates inflammation, which probably induces more PDGF-BB + preosteoclasts and type H vessel formation in callus, thereby promoting fracture healing. This study provides the evidence for the involvement of type H vessels in fracture healing and suggests the potential of A. muciniphila as a promising strategy for bone healing.This article has an associated First Person interview with the first author of the paper. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2020. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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