Neutrophils in Inflammatory Bone Diseases

Curr Osteoporos Rep. 2024 Apr;22(2):280-289. doi: 10.1007/s11914-024-00865-3. Epub 2024 Feb 29.

Abstract

Purpose of review: In this review, we summarize the current evidence that suggests that neutrophils play a key role in facilitating damage to local bone structures.

Recent findings: Neutrophil infiltration is a hallmark of inflammatory bone diseases such as rheumatoid arthritis (RA) and periodontitis disease (PD). Both of these human diseases are marked by an imbalance in bone homeostasis, favoring the degradation of local bone which ultimately leads to erosions. Osteoclasts, a multinucleated resident bone cell, are responsible for facilitating the turnover of bone and the bone damage observed in these diseases. The involvement of neutrophils and neutrophil extracellular trap formation have recently been implicated in exacerbating osteoclast function through direct and indirect mechanisms. We highlight a recent finding that NET proteins such as histones and elastase can generate non-canonical, inflammatory osteoclasts, and this process is mediated by post-translational modifications such as citrullination and carbamylation, both of which act as autoantigens in RA. It appears that NETs, autoantibodies, modified proteins, cytokines, and osteoclasts all ultimately contribute to local and permanent bone damage in RA and PD. However, more studies are needed to fully understand the role of neutrophils in inflammatory bone diseases.

Keywords: Carbamylation; Citrullination; Histones; NETs; Neutrophils; Osteoclast; Periodontitis; Rheumatoid arthritis.

Publication types

  • Review
  • Research Support, N.I.H., Intramural

MeSH terms

  • Arthritis, Rheumatoid* / immunology
  • Arthritis, Rheumatoid* / metabolism
  • Autoantibodies / immunology
  • Cytokines / immunology
  • Cytokines / metabolism
  • Extracellular Traps* / immunology
  • Extracellular Traps* / metabolism
  • Histones / metabolism
  • Humans
  • Neutrophil Infiltration
  • Neutrophils* / immunology
  • Osteoclasts* / metabolism
  • Periodontitis* / immunology
  • Periodontitis* / metabolism
  • Protein Processing, Post-Translational

Substances

  • Histones
  • Autoantibodies
  • Cytokines