Use of Therapeutic Pathogen Recognition Receptor Ligands for Osteo-Immunomodulation

Materials

卷:14

NadaR. Rahmani¹  Anne Kok¹  Harrie Weinans¹  MoyoC. Kruyt¹  Michiel Croes¹  Paree Khokhani¹  F.Cumhur Öner¹  Jacqueline Alblas¹ 

[1] Department of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands;

关键词: multifunctional coatings;    adjuvant;    osteoimmunology;    osteoblast;    osteoclast;    pathogen-recognition receptors;   

DOI  :  10.3390/ma14051119

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown