Membrane vesicles from Lactobacillus johnsonii delay osteoarthritis progression via modulating macrophage glutamine synthetase/mTORC1 axis

Aims: The manipulation of macrophage recruitment and their shift in the M1/M2 ratio is a promising approach to mitigate osteoarthritis (OA). Nevertheless, the current clinical medication available for OA is only palliative and may result in undesirable outcomes. Hence, it is urgent to explore altern...

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Main Authors: Rangru Liu, Yue Zhou, Huanxiong Chen, Haixia Xu, Min Zuo, Bo Chen, Hua Wang
Format: Article
Language:English
Published: Elsevier 2023-09-01
Series:Biomedicine & Pharmacotherapy
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0753332223009952
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author Rangru Liu
Yue Zhou
Huanxiong Chen
Haixia Xu
Min Zuo
Bo Chen
Hua Wang
author_facet Rangru Liu
Yue Zhou
Huanxiong Chen
Haixia Xu
Min Zuo
Bo Chen
Hua Wang
author_sort Rangru Liu
collection DOAJ
description Aims: The manipulation of macrophage recruitment and their shift in the M1/M2 ratio is a promising approach to mitigate osteoarthritis (OA). Nevertheless, the current clinical medication available for OA is only palliative and may result in undesirable outcomes. Hence, it is urgent to explore alternative disease-modifying drug supplement that are both safer and more effective in OA treatment, like probiotic and probiotic-derived membrane vesicles. Methods: The synovial inflammation and cartilage damage in collagenase-induced OA (CIOA) mice were observed using haematoxylin and eosin, saffron O-solid green and immunohistochemical staining. Bipedal balance test and open field test were conducted to determine the effectiveness of L. johnsonii-derived membrane vesicles (LJ-MVs) in reducing joint pain of CIOA mice. Additionally, Transwell, western blot, and immunological testing were used to examine the effect of LJ-MVs on macrophage migration and reprogramming. Furthermore, a 4D label-free proteomic analysis of LJ-MVs and their parent bacterium was performed, and the glutamine synthetase (GS)/mTORC1 axis in macrophage was verified by western blot. Results: L. johnsonii and its membrane vesicles, LJ-MVs, exhibit a novel ability to mitigate inflammation, cartilage damage, and pain associated with OA. This is achieved by their ability to impede macrophage migration, M1-like polarization, and inflammatory mediators secretion, while simultaneously promoting the M2/M1 ratio in synovial macrophages. The mechanism underlying this effect involves the modulation of macrophage GS/mTORC1 pathway, at least partially. Significance:: Owing to their probiotic derivation, LJ-MVs will be a more dependable and potent disease-modifying drugs for the prevention and therapy of OA in the long run.
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spelling doaj.art-9d6cb1bccf5c41d0926aa206d08eb8722023-08-13T04:53:00ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-09-01165115204Membrane vesicles from Lactobacillus johnsonii delay osteoarthritis progression via modulating macrophage glutamine synthetase/mTORC1 axisRangru Liu0Yue Zhou1Huanxiong Chen2Haixia Xu3Min Zuo4Bo Chen5Hua Wang6Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Tropical Medicine, Department of Spine Surgery of The First Affiliated Hospital, Hainan Medical University, Haikou, Hainan, China; Hainan Provincial Key Laboratory of R&D of Tropical Herbs, School of Pharmacy, Hainan Medical University, Haikou, Hainan, ChinaKey Laboratory of Tropical Translational Medicine of Ministry of Education, School of Tropical Medicine, Department of Spine Surgery of The First Affiliated Hospital, Hainan Medical University, Haikou, Hainan, ChinaDepartment of Spine Surgery, Hainan Province Clinical Medical Center, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, ChinaDepartment of Spine Surgery, Hainan Province Clinical Medical Center, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, ChinaKey Laboratory of Tropical Translational Medicine of Ministry of Education, School of Tropical Medicine, Department of Spine Surgery of The First Affiliated Hospital, Hainan Medical University, Haikou, Hainan, ChinaHainan Provincial Key Laboratory of R&D of Tropical Herbs, School of Pharmacy, Hainan Medical University, Haikou, Hainan, ChinaKey Laboratory of Tropical Translational Medicine of Ministry of Education, School of Tropical Medicine, Department of Spine Surgery of The First Affiliated Hospital, Hainan Medical University, Haikou, Hainan, China; Correspondence to: Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Tropical Medicine, Department of Spine Surgery of The First Affiliated Hospital, Hainan Medical University, Hainan Province Clinical Medical Center, Haikou 571199, China.Aims: The manipulation of macrophage recruitment and their shift in the M1/M2 ratio is a promising approach to mitigate osteoarthritis (OA). Nevertheless, the current clinical medication available for OA is only palliative and may result in undesirable outcomes. Hence, it is urgent to explore alternative disease-modifying drug supplement that are both safer and more effective in OA treatment, like probiotic and probiotic-derived membrane vesicles. Methods: The synovial inflammation and cartilage damage in collagenase-induced OA (CIOA) mice were observed using haematoxylin and eosin, saffron O-solid green and immunohistochemical staining. Bipedal balance test and open field test were conducted to determine the effectiveness of L. johnsonii-derived membrane vesicles (LJ-MVs) in reducing joint pain of CIOA mice. Additionally, Transwell, western blot, and immunological testing were used to examine the effect of LJ-MVs on macrophage migration and reprogramming. Furthermore, a 4D label-free proteomic analysis of LJ-MVs and their parent bacterium was performed, and the glutamine synthetase (GS)/mTORC1 axis in macrophage was verified by western blot. Results: L. johnsonii and its membrane vesicles, LJ-MVs, exhibit a novel ability to mitigate inflammation, cartilage damage, and pain associated with OA. This is achieved by their ability to impede macrophage migration, M1-like polarization, and inflammatory mediators secretion, while simultaneously promoting the M2/M1 ratio in synovial macrophages. The mechanism underlying this effect involves the modulation of macrophage GS/mTORC1 pathway, at least partially. Significance:: Owing to their probiotic derivation, LJ-MVs will be a more dependable and potent disease-modifying drugs for the prevention and therapy of OA in the long run.http://www.sciencedirect.com/science/article/pii/S0753332223009952Probiotic-derived membrane vesiclesSynovial macrophageMigrationReprogrammingLactobacillus johnsoniiChondrocyte anabolism
spellingShingle Rangru Liu
Yue Zhou
Huanxiong Chen
Haixia Xu
Min Zuo
Bo Chen
Hua Wang
Membrane vesicles from Lactobacillus johnsonii delay osteoarthritis progression via modulating macrophage glutamine synthetase/mTORC1 axis
Biomedicine & Pharmacotherapy
Probiotic-derived membrane vesicles
Synovial macrophage
Migration
Reprogramming
Lactobacillus johnsonii
Chondrocyte anabolism
title Membrane vesicles from Lactobacillus johnsonii delay osteoarthritis progression via modulating macrophage glutamine synthetase/mTORC1 axis
title_full Membrane vesicles from Lactobacillus johnsonii delay osteoarthritis progression via modulating macrophage glutamine synthetase/mTORC1 axis
title_fullStr Membrane vesicles from Lactobacillus johnsonii delay osteoarthritis progression via modulating macrophage glutamine synthetase/mTORC1 axis
title_full_unstemmed Membrane vesicles from Lactobacillus johnsonii delay osteoarthritis progression via modulating macrophage glutamine synthetase/mTORC1 axis
title_short Membrane vesicles from Lactobacillus johnsonii delay osteoarthritis progression via modulating macrophage glutamine synthetase/mTORC1 axis
title_sort membrane vesicles from lactobacillus johnsonii delay osteoarthritis progression via modulating macrophage glutamine synthetase mtorc1 axis
topic Probiotic-derived membrane vesicles
Synovial macrophage
Migration
Reprogramming
Lactobacillus johnsonii
Chondrocyte anabolism
url http://www.sciencedirect.com/science/article/pii/S0753332223009952
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