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Use of Therapeutic Pathogen Recognition Receptor Ligands for Osteo-Immunomodulation

Paree Khokhani1, Nada R Rahmani1, Anne Kok1

  • 1Department of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.

Materials (Basel, Switzerland)
|March 6, 2021
PubMed

Insights

Nucleic acid-based ligands promote early bone cell growth without excessive inflammation, showing promise for bone biomaterial coatings. These compounds enhance early bone formation markers while avoiding negative immune responses.

Area of Science:

  • Immunology
  • Biomaterials Science
  • Stem Cell Biology

Background:

  • Therapeutic pathogen recognition receptor (PRR) ligands modulate immune responses and are entering clinical use.
  • Understanding PRR ligand effects on bone cells and inflammation is crucial for developing effective biomaterials.

Purpose of the Study:

  • To investigate the impact of various therapeutic PRR ligands on human mesenchymal stem cell (hMSC) osteogenic differentiation and human monocyte inflammatory responses.
  • To identify PRR ligands that promote bone healing without adverse inflammatory effects for potential use in bone biomaterial coatings.

Main Methods:

  • hMSCs were stimulated with PRR ligands, and osteogenic differentiation was assessed via alkaline phosphatase (ALP) activity, osteocalcin, osteonectin expression, and calcium deposition.
  • Osteoclastogenesis was evaluated by measuring tartrate-resistant acid phosphatase (TRAP) activity in human monocytes.
  • Inflammatory cytokine (TNF-α, IL-6, IL-8, IL-10) expression was quantified using ELISA.

Main Results:

  • Nucleic acid-based ligands (Poly(I:C), CpG ODN C) significantly increased early ALP activity in hMSCs (4-fold) but did not affect later osteogenic markers or osteoclast formation.
  • Other tested ligands (MPLA, Curdlan, Pam3CSK4) did not influence osteogenic differentiation but inhibited monocyte TRAP activity, accompanied by increased pro-inflammatory cytokine expression.
  • Nucleic acid-based ligands demonstrated osteo-immunomodulatory potential by promoting early osteogenesis without significant inflammation or interference with osteoclastogenesis.

Conclusions:

  • Nucleic acid-based PRR ligands are promising candidates for osteo-immunomodulation, particularly for enhancing early bone formation.
  • These ligands offer a potential strategy for developing multifunctional bone biomaterial coatings that promote healing.
  • The findings highlight the selective immunomodulatory capacity of different PRR ligands in the context of bone regeneration.
Keywords:
adjuvantmultifunctional coatingsosteoblastosteoclastosteoimmunologypathogen-associated molecular patternspathogen-recognition receptors

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