High Concentrations of Polyelectrolyte Complex Nanoparticles Decrease Activity of Osteoclasts

Fracture treatment in osteoporotic patients is still challenging. Osteoporosis emerges when there is an imbalance between bone formation and resorption in favor of resorption by osteoclasts. Thus, new implant materials for osteoporotic fracture treatment should promote bone formation and reduce bone...

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Main Authors: Vivien Kauschke, Felix Maximilian Hessland, David Vehlow, Martin Müller, Christian Heiss, Katrin Susanne Lips
Format: Article
Language:English
Published: MDPI AG 2019-06-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/24/12/2346
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spelling doaj-2986367474294303a0d9ca870ce3cdf02020-11-25T01:13:36ZengMDPI AGMolecules1420-30492019-06-012412234610.3390/molecules24122346molecules24122346High Concentrations of Polyelectrolyte Complex Nanoparticles Decrease Activity of OsteoclastsVivien Kauschke0Felix Maximilian Hessland1David Vehlow2Martin Müller3Christian Heiss4Katrin Susanne Lips5Experimental Trauma Surgery, Justus-Liebig-University Giessen, Aulweg 128, 35392 Giessen, GermanyExperimental Trauma Surgery, Justus-Liebig-University Giessen, Aulweg 128, 35392 Giessen, GermanyLeibniz Institute of Polymer Research Dresden, Hohe Strasse 6, 01069 Dresden, GermanyLeibniz Institute of Polymer Research Dresden, Hohe Strasse 6, 01069 Dresden, GermanyExperimental Trauma Surgery, Justus-Liebig-University Giessen, Aulweg 128, 35392 Giessen, GermanyExperimental Trauma Surgery, Justus-Liebig-University Giessen, Aulweg 128, 35392 Giessen, GermanyFracture treatment in osteoporotic patients is still challenging. Osteoporosis emerges when there is an imbalance between bone formation and resorption in favor of resorption by osteoclasts. Thus, new implant materials for osteoporotic fracture treatment should promote bone formation and reduce bone resorption. Nanoparticles can serve as drug delivery systems for growth factors like Brain-Derived Neurotrophic Factor (BDNF), which stimulated osteoblast differentiation. Therefore, polyelectrolyte complex nanoparticles (PEC-NPs) consisting of poly(l-lysine) (PLL) and cellulose sulfate (CS), with or without addition of BDNF, were used to analyze their effect on osteoclasts in vitro. Live cell images showed that osteoclast numbers decreased after application of high PLL/CS PEC-NPs concentrations independent of whether BDNF was added or not. Real-time RT-PCR revealed that relative mRNA expression of cathepsin K and calcitonin receptor significantly declined after incubation of osteoclasts with high concentrations of PLL/CS PEC-NPs. Furthermore, Enzyme-Linked Immunosorbent Assay indicated that tartrate-resistant acidic phosphatase 5b activity was significantly reduced in the presence of high PLL/CS PEC-NPs concentrations. Consistent with these results, the pit formation analysis showed that less hydroxyapatite was resorbed by osteoclasts after incubation with high concentrations of PLL/CS PEC-NPs. BDNF had no influence on osteoclasts. We conclude that highly concentrated PLL/CS PEC-NPs dosages decreased osteoclastogenesis and osteoclasts activity. Moreover, BDNF might be a promising growth factor for osteoporotic fracture treatment since it did not increase osteoclast activity.https://www.mdpi.com/1420-3049/24/12/2346osteoclastspolyelectrolyte complex nanoparticlesBDNFdrug delivery systemcathepsin Kcalcitonin receptortartrate-resistant acidic phosphatase 5bpit formation
collection DOAJ
language English
format Article
sources DOAJ
author Vivien Kauschke
Felix Maximilian Hessland
David Vehlow
Martin Müller
Christian Heiss
Katrin Susanne Lips
spellingShingle Vivien Kauschke
Felix Maximilian Hessland
David Vehlow
Martin Müller
Christian Heiss
Katrin Susanne Lips
High Concentrations of Polyelectrolyte Complex Nanoparticles Decrease Activity of Osteoclasts
Molecules
osteoclasts
polyelectrolyte complex nanoparticles
BDNF
drug delivery system
cathepsin K
calcitonin receptor
tartrate-resistant acidic phosphatase 5b
pit formation
author_facet Vivien Kauschke
Felix Maximilian Hessland
David Vehlow
Martin Müller
Christian Heiss
Katrin Susanne Lips
author_sort Vivien Kauschke
title High Concentrations of Polyelectrolyte Complex Nanoparticles Decrease Activity of Osteoclasts
title_short High Concentrations of Polyelectrolyte Complex Nanoparticles Decrease Activity of Osteoclasts
title_full High Concentrations of Polyelectrolyte Complex Nanoparticles Decrease Activity of Osteoclasts
title_fullStr High Concentrations of Polyelectrolyte Complex Nanoparticles Decrease Activity of Osteoclasts
title_full_unstemmed High Concentrations of Polyelectrolyte Complex Nanoparticles Decrease Activity of Osteoclasts
title_sort high concentrations of polyelectrolyte complex nanoparticles decrease activity of osteoclasts
publisher MDPI AG
series Molecules
issn 1420-3049
publishDate 2019-06-01
description Fracture treatment in osteoporotic patients is still challenging. Osteoporosis emerges when there is an imbalance between bone formation and resorption in favor of resorption by osteoclasts. Thus, new implant materials for osteoporotic fracture treatment should promote bone formation and reduce bone resorption. Nanoparticles can serve as drug delivery systems for growth factors like Brain-Derived Neurotrophic Factor (BDNF), which stimulated osteoblast differentiation. Therefore, polyelectrolyte complex nanoparticles (PEC-NPs) consisting of poly(l-lysine) (PLL) and cellulose sulfate (CS), with or without addition of BDNF, were used to analyze their effect on osteoclasts in vitro. Live cell images showed that osteoclast numbers decreased after application of high PLL/CS PEC-NPs concentrations independent of whether BDNF was added or not. Real-time RT-PCR revealed that relative mRNA expression of cathepsin K and calcitonin receptor significantly declined after incubation of osteoclasts with high concentrations of PLL/CS PEC-NPs. Furthermore, Enzyme-Linked Immunosorbent Assay indicated that tartrate-resistant acidic phosphatase 5b activity was significantly reduced in the presence of high PLL/CS PEC-NPs concentrations. Consistent with these results, the pit formation analysis showed that less hydroxyapatite was resorbed by osteoclasts after incubation with high concentrations of PLL/CS PEC-NPs. BDNF had no influence on osteoclasts. We conclude that highly concentrated PLL/CS PEC-NPs dosages decreased osteoclastogenesis and osteoclasts activity. Moreover, BDNF might be a promising growth factor for osteoporotic fracture treatment since it did not increase osteoclast activity.
topic osteoclasts
polyelectrolyte complex nanoparticles
BDNF
drug delivery system
cathepsin K
calcitonin receptor
tartrate-resistant acidic phosphatase 5b
pit formation
url https://www.mdpi.com/1420-3049/24/12/2346
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