Abstract

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.

Highlights

  • Osteoclasts are an important cell type involved in bone metabolism

  • No differences were visible between cells that were incubated with or without Brain-Derived Neurotrophic Factor (BDNF) (Figure 1A,B)

  • Application of 40 μmol/L PLL/cellulose sulfate (CS) polyelectrolyte complex nanoparticles (PEC-NPs) without BDNF resulted in smaller multinucleated cells with less nuclei, ranging from 4–8 nuclei per cell and a higher amount of monocytes (Figure 1F)

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Summary

Introduction

Osteoclasts are an important cell type involved in bone metabolism. As an opponent to osteoblasts, they resorb bone in order to repair small defects and are involved in the remodeling process of aged parts of the bone matrix [1,2]. Bone formation is accomplished by osteoblasts [3]. During the bone formation process, osteoblasts immure themselves into the bone matrix where they differentiate into osteocytes [3]. Osteocytes are responsible for sensing the mechanical load and regulating bone modeling according to the mechanical needs of bone [4].

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