Print Email Facebook Twitter Use of therapeutic pathogen recognition receptor ligands for osteo-immunomodulation Title Use of therapeutic pathogen recognition receptor ligands for osteo-immunomodulation Author Khokhani, Paree (University Medical Center Utrecht) Rahmani, Nada R. (University Medical Center Utrecht) Kok, Anne (University Medical Center Utrecht) Öner, F. Cumhur (University Medical Center Utrecht) Alblas, Jacqueline (University Medical Center Utrecht) Weinans, Harrie (TU Delft Biomaterials & Tissue Biomechanics; University Medical Center Utrecht) Kruyt, Moyo C. (University Medical Center Utrecht) Croes, Michiel (University Medical Center Utrecht) Date 2021 Abstract Therapeutic pathogen recognition receptor (PRR) ligands are reaching clinical practice following their ability to skew the immune response in a specific direction. We investigated the effects of various therapeutic PRR ligands on bone cell differentiation and inflammation. Following stimu-lation, alkaline phosphatase (ALP) activity (Day 10), osteocalcin, osteonectin expression (Day 14), and calcium deposition (Day 21) were quantified in bone marrow-derived human mesenchymal stem cells (hMSCs). The osteoclastogenic response was determined by measuring tartrate-resistant acid phosphate (TRAP) activity in human monocytes. TNF-α, IL-6, IL-8, and IL-10 expressions were measured by enzyme-linked immunosorbent assay as an indicator of the ligands’ inflammatory properties. We found that nucleic acid-based ligands Poly(I:C) and CpG ODN C increased early ALP activity in hMSCs by 4-fold without affecting osteoclast formation. These ligands did not enhance expression of the other, late osteogenic markers. MPLA, Curdlan, and Pam3CSK4 did not affect osteogenic differentiation, but inhibited TRAP activity in monocytes, which was associated with increased expression of all measured cytokines. Nucleic acid-based ligands are identified as the most promising osteo-immunomodulators, as they favor early osteogenic differentiation without inducing an exaggerated immune-cell mediated response or interfering in osteoclastogenesis and thus can be potentially harnessed for multifunctional coatings for bone biomaterials. Subject AdjuvantMultifunctional coatingsOsteoblastOsteoclastOsteoimmunologyPathogen-associated molecular patternsPathogen-recognition receptors To reference this document use: http://resolver.tudelft.nl/uuid:d05b81c4-974c-44cf-8ca1-dbffc0c86149 DOI https://doi.org/10.3390/ma14051119 ISSN 1996-1944 Source Materials, 14 (5) Part of collection Institutional Repository Document type journal article Rights © 2021 Paree Khokhani, Nada R. Rahmani, Anne Kok, F. Cumhur Öner, Jacqueline Alblas, Harrie Weinans, Moyo C. Kruyt, Michiel Croes Files PDF materials_14_01119_v2.pdf 1.95 MB Close viewer /islandora/object/uuid:d05b81c4-974c-44cf-8ca1-dbffc0c86149/datastream/OBJ/view