Use of Therapeutic Pathogen Recognition Receptor Ligands for Osteo-Immunomodulation
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 stimulation, alk...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-02-01
|
| Series: | Materials |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1996-1944/14/5/1119 |
| _version_ | 1797417284597186560 |
|---|---|
| author | Paree Khokhani Nada R. Rahmani Anne Kok F. Cumhur Öner Jacqueline Alblas Harrie Weinans Moyo C. Kruyt Michiel Croes |
| author_facet | Paree Khokhani Nada R. Rahmani Anne Kok F. Cumhur Öner Jacqueline Alblas Harrie Weinans Moyo C. Kruyt Michiel Croes |
| author_sort | Paree Khokhani |
| collection | DOAJ |
| description | 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 stimulation, 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. |
| first_indexed | 2024-03-09T06:16:28Z |
| format | Article |
| id | doaj.art-3cc71d31bec74562a1936d6242732c7b |
| institution | Directory Open Access Journal |
| issn | 1996-1944 |
| language | English |
| last_indexed | 2024-03-09T06:16:28Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Materials |
| spelling | doaj.art-3cc71d31bec74562a1936d6242732c7b2023-12-03T11:52:45ZengMDPI AGMaterials1996-19442021-02-01145111910.3390/ma14051119Use of Therapeutic Pathogen Recognition Receptor Ligands for Osteo-ImmunomodulationParee Khokhani0Nada R. Rahmani1Anne Kok2F. Cumhur Öner3Jacqueline Alblas4Harrie Weinans5Moyo C. Kruyt6Michiel Croes7Department of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDepartment of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDepartment of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDepartment of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDepartment of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDepartment of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDepartment of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDepartment of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsTherapeutic 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 stimulation, 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.https://www.mdpi.com/1996-1944/14/5/1119multifunctional coatingsadjuvantosteoimmunologyosteoblastosteoclastpathogen-recognition receptors |
| spellingShingle | Paree Khokhani Nada R. Rahmani Anne Kok F. Cumhur Öner Jacqueline Alblas Harrie Weinans Moyo C. Kruyt Michiel Croes Use of Therapeutic Pathogen Recognition Receptor Ligands for Osteo-Immunomodulation Materials multifunctional coatings adjuvant osteoimmunology osteoblast osteoclast pathogen-recognition receptors |
| title | Use of Therapeutic Pathogen Recognition Receptor Ligands for Osteo-Immunomodulation |
| title_full | Use of Therapeutic Pathogen Recognition Receptor Ligands for Osteo-Immunomodulation |
| title_fullStr | Use of Therapeutic Pathogen Recognition Receptor Ligands for Osteo-Immunomodulation |
| title_full_unstemmed | Use of Therapeutic Pathogen Recognition Receptor Ligands for Osteo-Immunomodulation |
| title_short | Use of Therapeutic Pathogen Recognition Receptor Ligands for Osteo-Immunomodulation |
| title_sort | use of therapeutic pathogen recognition receptor ligands for osteo immunomodulation |
| topic | multifunctional coatings adjuvant osteoimmunology osteoblast osteoclast pathogen-recognition receptors |
| url | https://www.mdpi.com/1996-1944/14/5/1119 |
| work_keys_str_mv | AT pareekhokhani useoftherapeuticpathogenrecognitionreceptorligandsforosteoimmunomodulation AT nadarrahmani useoftherapeuticpathogenrecognitionreceptorligandsforosteoimmunomodulation AT annekok useoftherapeuticpathogenrecognitionreceptorligandsforosteoimmunomodulation AT fcumhuroner useoftherapeuticpathogenrecognitionreceptorligandsforosteoimmunomodulation AT jacquelinealblas useoftherapeuticpathogenrecognitionreceptorligandsforosteoimmunomodulation AT harrieweinans useoftherapeuticpathogenrecognitionreceptorligandsforosteoimmunomodulation AT moyockruyt useoftherapeuticpathogenrecognitionreceptorligandsforosteoimmunomodulation AT michielcroes useoftherapeuticpathogenrecognitionreceptorligandsforosteoimmunomodulation |