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

V Ulici1, K L Kelley1, M A Azcarate-Peril2

  • 1Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Abstract

Insights

The gut microbiota influences osteoarthritis (OA) development after joint injury. Germ-free mice showed reduced OA severity compared to specific pathogen-free mice, indicating microbial factors promote disease.

Area of Science:

  • Orthopedics
  • Microbiology
  • Immunology

Background:

  • Osteoarthritis (OA) is a degenerative joint disease with complex etiology.
  • The role of the gut microbiota in OA pathogenesis remains incompletely understood.

Purpose of the Study:

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

Main Methods:

  • Osteoarthritis was induced using the destabilized medial meniscus (DMM) model in germ-free (GF) and specific pathogen-free (SPF) mice.
  • OA severity was assessed via articular cartilage structure (ACS), safranin O (SafO) staining, osteophyte size, and synovial hyperplasia.
  • Microbiome composition was analyzed using 16S rRNA sequencing; plasma lipopolysaccharide (LPS) and LPS binding protein (LBP) were measured.

Main Results:

  • GF DMM mice exhibited significantly lower maximum ACS scores (28% reduction) and SafO sum scores (31% reduction) compared to SPF DMM mice.
  • These protective effects were more pronounced in younger GF DMM mice, which also showed reduced osteophyte size (36%) and LBP levels (27%).
  • Distinct Operational Taxonomic Unit (OTU) abundances correlated with OA severity in SPF mice.

Conclusions:

  • Factors associated with the gut microbiota promote the development of osteoarthritis following joint injury.
  • Targeting the gut microbiota may offer a therapeutic strategy for preventing or treating OA.

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