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Osteoarthritis Cartilage. 2018 Aug;26(8):1098-1109. doi: 10.1016/j.joca.2018.05.016. Epub 2018 May 30.

Osteoarthritis induced by destabilization of the medial meniscus is reduced in germ-free mice.

Author information

1
Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
2
Department of Medicine, Division of Gastroenterology and Hepatology, and Microbiome Core Facility, Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
3
Department of Medicine, Division of Gastroenterology and Hepatology and Gnotobiotic Core Facility, Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
4
Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
5
Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: richard_loeser@med.unc.edu.

Abstract

OBJECTIVE:

To determine the contribution of the gut microbiota to the development of injury-induced osteoarthritis (OA).

DESIGN:

OA was induced using the destabilized medial meniscus (DMM) model in 20 germ-free (GF) C57BL/6J male mice housed in a gnotobiotic facility and 23 strain-matched specific pathogen free (SPF) mice in 2 age groups -13.5 weeks avg age at DMM (17 SPF and 15 GF) and 43 weeks avg age at DMM (6 SPF and 5 GF). OA severity was measured using scores for articular cartilage structure (ACS), loss of safranin O (SafO) staining, osteophyte size, and synovial hyperplasia. Microbiome analysis by 16S rRNA amplicon sequencing was performed on stool samples and LPS and LPS binding protein (LBP) were measured in plasma.

RESULTS:

Compared to the SPF DMM mice, the maximum (MAX) ACS score per joint was 28% lower (p = 0.036) in GF DMM mice while the SafO sum score of all sections evaluated per joint was decreased by 31% (p = 0.009). The differences between SPF and GF mice in these scores were greater when only the younger mice were included in the analysis. The younger GF DMM mice also had significant reductions in osteophyte size (36%, P = 0.0119) and LBP (27%, P = 0.007) but not synovial scores or LPS. Differences in relative abundance of a number of Operational Taxonomic Units (OTUs) were noted between SPF mice with high vs low maximum ACS scores.

CONCLUSIONS:

These results suggest factors related to the gut microbiota promote the development of OA after joint injury.

KEYWORDS:

Cartilage; DMM; Germ-free; LBP; Microbiome; Osteoarthritis

PMID:
29857156
DOI:
10.1016/j.joca.2018.05.016
[Indexed for MEDLINE]
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