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Open AccessArticle

Antibiotic Treatment Prior to Injury Improves Post-Traumatic Osteoarthritis Outcomes in Mice

1
Lawrence Livermore National Laboratories, Physical and Life Sciences Directorate, Livermore, CA 94550, USA
2
UC Merced, School of Natural Sciences, Merced, CA 95343, USA
3
UC Davis Medical Center, Department of Orthopedic Surgery, Sacramento, CA 95817, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(17), 6424; https://doi.org/10.3390/ijms21176424
Received: 24 July 2020 / Revised: 28 August 2020 / Accepted: 29 August 2020 / Published: 3 September 2020
(This article belongs to the Special Issue Research of Pathogenesis and Novel Therapeutics in Arthritis 2.0)
Osteoarthritis (OA) is a painful and debilitating disease characterized by the chronic and progressive degradation of articular cartilage. Post-traumatic OA (PTOA) is a secondary form of OA that develops in ~50% of cases of severe articular injury. Inflammation and re-occurring injury have been implicated as contributing to the progression of PTOA after the initial injury. However, there is very little known about external factors prior to injury that could affect the risk of PTOA development. To examine how the gut microbiome affects PTOA development we used a chronic antibiotic treatment regimen starting at weaning for six weeks prior to ACL rupture, in mice. A six-weeks post-injury histological examination showed more robust cartilage staining on the antibiotic (AB)-treated mice than the untreated controls (VEH), suggesting slower disease progression in AB cohorts. Injured joints also showed an increase in the presence of anti-inflammatory M2 macrophages in the AB group. Molecularly, the phenotype correlated with a significantly lower expression of inflammatory genes Tlr5, Ccl8, Cxcl13, and Foxo6 in the injured joints of AB-treated animals. Our results indicate that a reduced state of inflammation at the time of injury and a lower expression of Wnt signaling modulatory protein, Rspo1, caused by AB treatment can slow down or improve PTOA outcomes. View Full-Text
Keywords: osteoarthritis; PTOA; gene expression; RNA-seq; cartilage degeneration; tibial compression; gut microbiome; antibiotics; LPS osteoarthritis; PTOA; gene expression; RNA-seq; cartilage degeneration; tibial compression; gut microbiome; antibiotics; LPS
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Mendez, M.E.; Murugesh, D.K.; Sebastian, A.; Hum, N.R.; McCloy, S.A.; Kuhn, E.A.; Christiansen, B.A.; Loots, G.G. Antibiotic Treatment Prior to Injury Improves Post-Traumatic Osteoarthritis Outcomes in Mice. Int. J. Mol. Sci. 2020, 21, 6424.

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