Scientific article
Open access

NADPH oxidase 4 deficiency attenuates experimental osteoarthritis in mice

Published inRMD open, vol. 9, no. 1, e002856
Publication date2023-02-21

Objective: Low-grade inflammation plays a pivotal role in osteoarthritis (OA) through exposure to reactive oxygen species (ROS). In chondrocytes, NADPH oxidase 4 (NOX4) is one of the major ROS producers. In this study, we evaluated the role of NOX4 on joint homoeostasis after destabilisation of the medial meniscus (DMM) in mice.

Methods: Experimental OA was simulated on cartilage explants using interleukin-1β (IL-1β) and induced by DMM in wild-type (WT) and NOX4 knockout (NOX4-/-) mice. We evaluated NOX4 expression, inflammation, cartilage metabolism and oxidative stress by immunohistochemistry. Bone phenotype was also determined by micro-CT and histomorphometry.

Results: Whole body NOX4 deletion attenuated experimental OA in mice, with a significant reduction of the OARSI score at 8 weeks. DMM increased total subchondral bone plate (SB.Th), epiphysial trabecular thicknesses (Tb.Th) and bone volume fraction (BV/TV) in both NOX4-/-and wild-type (WT) mice. Interestingly, DDM decreased total connectivity density (Conn.Dens) and increased medial BV/TV and Tb.Th only in WT mice. Ex vivo, NOX4 deficiency increased aggrecan (AGG) expression and decreased matrix metalloproteinase 13 (MMP13) and collagen type I (COL1) expression. IL-1β increased NOX4 and 8-hydroxy-2'-deoxyguanosine (8-OHdG) expression in WT cartilage explants but not in NOX4-/-. In vivo, absence of NOX4 increased anabolism and decreased catabolism after DMM. Finally, NOX4 deletion decreased synovitis score, 8-OHdG and F4/80 staining following DMM.

Conclusion: NOX4 deficiency restores cartilage homoeostasis, inhibits oxidative stress, inflammation and delays OA progression after DMM in mice. These findings suggest that NOX4 represent a potential target to counteract for OA treatment.

  • Cytokines
  • Inflammation
  • Osteoarthritis
  • Animals
  • Mice
  • Disease Models, Animal
  • NADPH Oxidase 4 / deficiency
  • NADPH Oxidase 4 / genetics
  • Osteoarthritis / genetics
  • Reactive Oxygen Species
  • Mice, Knockout
Citation (ISO format)
RENAUDIN, Félix et al. NADPH oxidase 4 deficiency attenuates experimental osteoarthritis in mice. In: RMD open, 2023, vol. 9, n° 1, p. e002856. doi: 10.1136/rmdopen-2022-002856
Main files (1)
Article (Published version)
ISSN of the journal2056-5933

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Creation03/02/2023 2:40:08 PM
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