CD14+ monocytes contribute to inflammation in chronic nonbacterial osteomyelitis (CNO) through increased NLRP3

D Brandt1, E Sohr1, J Pablik2

  • 1Klinik und Poliklinik für Kinder- und Jugendmedizin, Universitätsklinikum Carl Gustav Carus, TU Dresden, Dresden, Germany.

Insights

Monocytes play a key role in chronic nonbacterial osteomyelitis (CNO) inflammation. Increased NLRP3 inflammasome activation in monocytes, linked to DNA hypomethylation, suggests they are crucial drivers of this bone disease.

Area of Science:

  • Immunology
  • Genetics
  • Pathophysiology

Background:

  • Chronic nonbacterial osteomyelitis (CNO) pathophysiology is not fully understood.
  • Increased NLRP3 inflammasome activation and IL-1β release in monocytes are implicated in CNO bone inflammation.

Purpose of the Study:

  • To investigate the role of immune cell infiltrates, particularly monocytes, in CNO across different disease stages.
  • To explore the link between inflammasome component expression, DNA methylation, and monocyte involvement in CNO.

Main Methods:

  • Analysis of immune cell infiltrates in CNO bone lesions.
  • Assessment of inflammasome component (NLRP3, ASC) gene expression in monocytes.
  • DNA methylation analysis of NLRP3 and PYCARD genes in monocytes.

Main Results:

  • Monocytes are consistently involved in CNO at all disease stages, unlike other immune cells.
  • Increased expression of NLRP3 and ASC inflammasome components was observed in monocytes.
  • Site-specific DNA hypomethylation around NLRP3 and PYCARD genes correlated with increased inflammasome component expression.

Conclusions:

  • Pro-inflammatory monocytes are central to CNO pathophysiology.
  • Monocyte-derived NLRP3 inflammasome activation, potentially driven by DNA hypomethylation, contributes to bone inflammation in CNO.
  • Identified cellular and molecular alterations in monocytes may serve as potential biomarkers or therapeutic targets for CNO.

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