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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Elsevier
2023-09-01
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Series: | Biomedicine & Pharmacotherapy |
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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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language | English |
last_indexed | 2024-03-12T15:04:35Z |
publishDate | 2023-09-01 |
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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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