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The microbiome mediates subchondral bone loss and metabolomic changes after acute joint trauma

Alyssa K. Hahn, Cameron W. Wallace, Hope D. Welhaven, Ellen Brooks, Mark McAlpine, Blaine A. Christiansen, Seth T. Walk, View ORCID ProfileRonald K. June
doi: https://doi.org/10.1101/2020.05.08.084822
Alyssa K. Hahn
1Department of Biology, Carroll College, Helena, MT596225
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Cameron W. Wallace
2WWAMI Medical School, Montana State University, Bozeman, MT 59718
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Hope D. Welhaven
1Department of Biology, Carroll College, Helena, MT596225
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Ellen Brooks
3Department of Chemical & Biological Engineering, Montana State University, Bozeman, MT 59717
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Mark McAlpine
4Department of Microbiology & Immunology, Montana State University, Bozeman, MT 59717
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Blaine A. Christiansen
5Department of Orthopaedic Surgery, University of California Davis, Sacramento, CA 95817
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Seth T. Walk
4Department of Microbiology & Immunology, Montana State University, Bozeman, MT 59717
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Ronald K. June
4Department of Microbiology & Immunology, Montana State University, Bozeman, MT 59717
6Department of Mechanical & Industrial Engineering, Montana State University, Bozeman, MT 59717
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  • ORCID record for Ronald K. June
  • For correspondence: rkjune@gmail.com
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Abstract

Objective To compare the early responses to joint injury in conventional and germ-free mice.

Design Post traumatic osteoarthritis PTOA was induced using a non-invasive anterior cruciate ligament rupture model in 20-week old germ-free (GF) and conventional C57BL/6 mice. Injury was induced in the left knees of n=8 GF and n=10 conventional mice. To examine the effects of injury, n=5 GF and n=9 conventional control mice were used. Mice were euthanized seven days post-injury, followed by synovial fluid recovery for global metabolomic profiling and analysis of epiphyseal trabecular bone by micro-computed tomography (μCT). Global metabolomic profiling assessed metabolic differences in the joint response to injury between GF and conventional mice. Magnitude of trabecular bone volume loss measured using μCT assessed early OA progression in GF and conventional mice.

Results μCT found that GF mice had significantly less trabecular bone loss compared to conventional mice, indicating that the GF status was protective against early OA changes in bone structure. Global metabolomic profiling showed that conventional mice had greater variability in their metabolic response to injury, and a more distinct joint metabolome compared to their corresponding controls. Furthermore, differences in the response to injury in GF compared to conventional mice were linked to mouse metabolic pathways that regulate inflammation associated with the innate immune system.

Conclusions These results suggest that the gut microbiota promote the development of PTOA during the acute phase following joint trauma possibly through the regulation of the innate immune system.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 09, 2020.
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The microbiome mediates subchondral bone loss and metabolomic changes after acute joint trauma
Alyssa K. Hahn, Cameron W. Wallace, Hope D. Welhaven, Ellen Brooks, Mark McAlpine, Blaine A. Christiansen, Seth T. Walk, Ronald K. June
bioRxiv 2020.05.08.084822; doi: https://doi.org/10.1101/2020.05.08.084822
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The microbiome mediates subchondral bone loss and metabolomic changes after acute joint trauma
Alyssa K. Hahn, Cameron W. Wallace, Hope D. Welhaven, Ellen Brooks, Mark McAlpine, Blaine A. Christiansen, Seth T. Walk, Ronald K. June
bioRxiv 2020.05.08.084822; doi: https://doi.org/10.1101/2020.05.08.084822

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