Multinucleated giant cells with an osteoclast phenotype derived from caprine peripheral blood mononuclear cells

Giuliano Pisoni1, Patrizia D'Amelio, Francesca Sassi

  • 1Università degli Studi di Milano, Dipartimento di Patologia Animale, Igiene e Sanità Pubblica Veterinaria, via Celoria 10, 20133 Milano, Italy. giuliano.pisoni@unimi.it

Insights

Multinucleated giant cells (MGCs) formed in healthy goats, challenging their use as a diagnostic marker for small ruminant lentivirus (SRLV) infection. These MGCs exhibited osteoclast characteristics, suggesting a novel pathway independent of SRLV.

Area of Science:

  • Veterinary Virology
  • Cell Biology
  • Immunology

Background:

  • Macrophage fusion forming multinucleated giant cells (MGCs) is a known cytopathic effect of lentiviral replication.
  • MGC formation in caprine peripheral blood mononuclear cells (PBMCs) has been a diagnostic indicator for small ruminant lentivirus (SRLV) infection.

Purpose of the Study:

  • To investigate MGC formation in healthy goats not infected with SRLV.
  • To characterize the phenotype of MGCs derived from healthy caprine PBMCs.

Main Methods:

  • Culturing PBMCs from SRLV-free goats.
  • Observing MGC formation over 7-14 days.
  • Assessing MGC expression of tartrate-resistant acid phosphatase, calcitonin receptor, integrin αVβ3, cathepsin K, and matrix metalloproteinase 9.
  • Evaluating in vitro bone resorption capacity.

Main Results:

  • MGCs formed in cultures from healthy goats within 7-14 days.
  • These MGCs expressed key osteoclast markers (TRAP, calcitonin receptor, integrin αVβ3, cathepsin K, MMP-9).
  • The MGCs demonstrated in vitro bone resorption activity without RANKL or M-CSF.

Conclusions:

  • MGC formation occurs in healthy goats, indicating it is not exclusively a marker for SRLV infection.
  • Caprine MGCs possess an osteoclast-like phenotype and function independently of typical osteoclastogenic factors.
  • Re-evaluation of MGCs as a sole diagnostic criterion for SRLV infection is warranted.

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