Cargando…
Osteogenic Effect of Pregabalin in Human Primary Mesenchymal Stem Cells, Osteoblasts, and Osteosarcoma Cells
Seventy million patients worldwide are suffering from epilepsy. The long-term use of antiepileptic drugs causes the alteration of the bone tissue and its metabolism, thus increasing the risk of fractures. Clinical and pre-clinical studies have highlighted conflicting data on the influence of the rel...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032037/ https://www.ncbi.nlm.nih.gov/pubmed/35454987 http://dx.doi.org/10.3390/life12040496 |
_version_ | 1784692541302505472 |
---|---|
author | Wagener, Nele Di Fazio, Pietro Böker, Kai Oliver Matziolis, Georg |
author_facet | Wagener, Nele Di Fazio, Pietro Böker, Kai Oliver Matziolis, Georg |
author_sort | Wagener, Nele |
collection | PubMed |
description | Seventy million patients worldwide are suffering from epilepsy. The long-term use of antiepileptic drugs causes the alteration of the bone tissue and its metabolism, thus increasing the risk of fractures. Clinical and pre-clinical studies have highlighted conflicting data on the influence of the relatively new antiepileptic drug pregabalin (Lyrica(®)). The objective of the present study was therefore to investigate its cytotoxicity in primary human osteoblasts (hOB). HOB and human mesenchymal stem cells (hMSC) were isolated from patients. The human osteosarcoma cells MG63 were included as established cell line. Cells were incubated with pregabalin at concentrations ranging from 0 to 40 μg/mL. Time-dependent cell proliferation was measured by automatic cell counting, and metabolism was determined by XTT assay and osseous differentiation by alkaline phosphatase (ALP) activity. Histological examinations of calcium deposit were performed with ALP, Alizarin Red, and von Kossa staining. A concentration-dependent increase in the proliferation of hOB and hMSC was observed after treatment with pregabalin. All cells showed a significant increase in cell metabolism. The osteogenic differentiation, confirmed by the increase of calcium deposit, was promoted by the administration of pregabalin. This effect was already significant at the therapeutic plasma concentration of pregabalin (10 μg/mL). In contrast to the other antiepileptic drugs, pregabalin showed no osteocatabolic effects. Conflicting in-vivo data must therefore be attributed to systemic effects of pregabalin. |
format | Online Article Text |
id | pubmed-9032037 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90320372022-04-23 Osteogenic Effect of Pregabalin in Human Primary Mesenchymal Stem Cells, Osteoblasts, and Osteosarcoma Cells Wagener, Nele Di Fazio, Pietro Böker, Kai Oliver Matziolis, Georg Life (Basel) Article Seventy million patients worldwide are suffering from epilepsy. The long-term use of antiepileptic drugs causes the alteration of the bone tissue and its metabolism, thus increasing the risk of fractures. Clinical and pre-clinical studies have highlighted conflicting data on the influence of the relatively new antiepileptic drug pregabalin (Lyrica(®)). The objective of the present study was therefore to investigate its cytotoxicity in primary human osteoblasts (hOB). HOB and human mesenchymal stem cells (hMSC) were isolated from patients. The human osteosarcoma cells MG63 were included as established cell line. Cells were incubated with pregabalin at concentrations ranging from 0 to 40 μg/mL. Time-dependent cell proliferation was measured by automatic cell counting, and metabolism was determined by XTT assay and osseous differentiation by alkaline phosphatase (ALP) activity. Histological examinations of calcium deposit were performed with ALP, Alizarin Red, and von Kossa staining. A concentration-dependent increase in the proliferation of hOB and hMSC was observed after treatment with pregabalin. All cells showed a significant increase in cell metabolism. The osteogenic differentiation, confirmed by the increase of calcium deposit, was promoted by the administration of pregabalin. This effect was already significant at the therapeutic plasma concentration of pregabalin (10 μg/mL). In contrast to the other antiepileptic drugs, pregabalin showed no osteocatabolic effects. Conflicting in-vivo data must therefore be attributed to systemic effects of pregabalin. MDPI 2022-03-28 /pmc/articles/PMC9032037/ /pubmed/35454987 http://dx.doi.org/10.3390/life12040496 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wagener, Nele Di Fazio, Pietro Böker, Kai Oliver Matziolis, Georg Osteogenic Effect of Pregabalin in Human Primary Mesenchymal Stem Cells, Osteoblasts, and Osteosarcoma Cells |
title | Osteogenic Effect of Pregabalin in Human Primary Mesenchymal Stem Cells, Osteoblasts, and Osteosarcoma Cells |
title_full | Osteogenic Effect of Pregabalin in Human Primary Mesenchymal Stem Cells, Osteoblasts, and Osteosarcoma Cells |
title_fullStr | Osteogenic Effect of Pregabalin in Human Primary Mesenchymal Stem Cells, Osteoblasts, and Osteosarcoma Cells |
title_full_unstemmed | Osteogenic Effect of Pregabalin in Human Primary Mesenchymal Stem Cells, Osteoblasts, and Osteosarcoma Cells |
title_short | Osteogenic Effect of Pregabalin in Human Primary Mesenchymal Stem Cells, Osteoblasts, and Osteosarcoma Cells |
title_sort | osteogenic effect of pregabalin in human primary mesenchymal stem cells, osteoblasts, and osteosarcoma cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032037/ https://www.ncbi.nlm.nih.gov/pubmed/35454987 http://dx.doi.org/10.3390/life12040496 |
work_keys_str_mv | AT wagenernele osteogeniceffectofpregabalininhumanprimarymesenchymalstemcellsosteoblastsandosteosarcomacells AT difaziopietro osteogeniceffectofpregabalininhumanprimarymesenchymalstemcellsosteoblastsandosteosarcomacells AT bokerkaioliver osteogeniceffectofpregabalininhumanprimarymesenchymalstemcellsosteoblastsandosteosarcomacells AT matziolisgeorg osteogeniceffectofpregabalininhumanprimarymesenchymalstemcellsosteoblastsandosteosarcomacells |