Antibiotic Treatment Prior to Injury Abrogates the Detrimental Effects of LPS in STR/ort Mice Susceptible to Osteoarthritis Development
[1];
[1];
[2];
[3]
- Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
- University of California Davis Health, Sacramento, CA (United States)
- Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States); University of California Davis Health, Sacramento, CA (United States)
Post traumatic osteoarthritis (PTOA) is a form of secondary osteoarthritis (OA) that develops in ~50% of cases of severe articular joint injuries and leads to chronic and progressive degradation of articular cartilage and other joint tissues. PTOA progression can be exacerbated by repeated injury and systemic inflammation. Few studies have examined approaches for blunting or slowing down PTOA progression with emphasis on systemic inflammation; most arthritis studies focused on the immune system have been in the context of rheumatoid arthritis. To examine how the gut microbiome affects systemic inflammation during PTOA development, we used a chronic antibiotic treatment regimen starting at weaning for 6 weeks before anterior cruciate ligament (ACL) rupture in STR/ort mice combined with lipopolysaccharide (LPS)-induced systemic inflammation. STR/ort mice develop spontaneous OA as well as a more severe PTOA phenotype than C57Bl/6J mice. By 6 weeks post injury, histological examination showed a more robust cartilage staining in the antibiotic-treated (AB) STR/ort mice than in the untreated STR/ort controls. Furthermore, we also examined the effects of AB treatment on systemic inflammation and found that the effects of LPS administration before injury are also blunted by AB treatment in STR/ort mice. The AB- or AB+LPS-treated STR/ort injured joints more closely resembled the C57Bl/6J VEH OA phenotypes than the vehicle- or LPS-treated STR/ort, suggesting that antibiotic treatment has the potential to slow disease progression and should be further explored therapeutically as prophylactic post injury.
- Research Organization:
- Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
- Sponsoring Organization:
- USDOE National Nuclear Security Administration (NNSA)
- Grant/Contract Number:
- AC52-07NA27344
- OSTI ID:
- 1999738
- Report Number(s):
- LLNL-JRNL--849212; 1074696
- Journal Information:
- JBMR Plus, Journal Name: JBMR Plus Journal Issue: 8 Vol. 7; ISSN 2473-4039
- Publisher:
- Wiley - American Society for Bone and Mineral ResearchCopyright Statement
- Country of Publication:
- United States
- Language:
- English
Similar Records
Comparative Transcriptomics Identifies Novel Genes and Pathways Involved in Post-Traumatic Osteoarthritis Development and Progression
Global Gene Expression Differences in Joints of Mice with Divergent Post Traumatic Osteoarthritis Phenotypes