Dose-Dependent Effects of a Novel Selective EP<sub>4</sub> Prostaglandin Receptor Agonist on Treatment of Critical Size Femoral Bone Defects in a Rat Model

Difficulties in treating pseudarthrosis and critical bone defects are still evident in physicians’ clinical routines. Bone morphogenetic protein 2 (BMP-2) has shown promising osteoinductive results but also considerable side effects, not unexpected given that it is a morphogen. Thus, the bone regene...

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Autores principales:	Corina Vater, Elisabeth Mehnert, Henriette Bretschneider, Julia Bolte, Lisa Findeisen, Lucas-Maximilian Matuszewski, Stefan Zwingenberger
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	critical-sized bone defect bone regeneration tissue regeneration scaffold EP<sub>4</sub> receptor agonist BMP-2 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/71d9ae15f7874ec19e2ad0652a02c8b8
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spelling	oai:doaj.org-article:71d9ae15f7874ec19e2ad0652a02c8b82021-11-25T16:51:09ZDose-Dependent Effects of a Novel Selective EP<sub>4</sub> Prostaglandin Receptor Agonist on Treatment of Critical Size Femoral Bone Defects in a Rat Model10.3390/biomedicines91117122227-9059https://doaj.org/article/71d9ae15f7874ec19e2ad0652a02c8b82021-11-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1712https://doaj.org/toc/2227-9059Difficulties in treating pseudarthrosis and critical bone defects are still evident in physicians’ clinical routines. Bone morphogenetic protein 2 (BMP-2) has shown promising osteoinductive results but also considerable side effects, not unexpected given that it is a morphogen. Thus, the bone regenerative potential of the novel selective, non-morphogenic EP<sub>4</sub> prostaglandin receptor agonist KMN-159 was investigated in this study. Therefore, mineralized collagen type-1 matrices were loaded with different amounts of BMP-2 or KMN-159 and implanted into a 5 mm critical-sized femoral defect in rats. After 12 weeks of observation, micro-computed tomography scans were performed to analyze the newly formed bone volume (BV) and bone mineral density (BMD). Histological analysis was performed to evaluate the degree of defect healing and the number of vessels, osteoclasts, and osteoblasts. Data were evaluated using Kruskal-Wallis followed by Dunn’s post hoc test. As expected, animals treated with BMP-2, the positive control for this model, showed a high amount of newly formed BV as well as bone healing. For KMN-159, a dose-dependent effect on bone regeneration could be observed up to a dose optimum, demonstrating that this non-morphogenic mechanism of action can stimulate bone formation in this model system.Corina VaterElisabeth MehnertHenriette BretschneiderJulia BolteLisa FindeisenLucas-Maximilian MatuszewskiStefan ZwingenbergerMDPI AGarticlecritical-sized bone defectbone regenerationtissue regenerationscaffoldEP<sub>4</sub> receptor agonistBMP-2Biology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1712, p 1712 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	critical-sized bone defect bone regeneration tissue regeneration scaffold EP<sub>4</sub> receptor agonist BMP-2 Biology (General) QH301-705.5
spellingShingle	critical-sized bone defect bone regeneration tissue regeneration scaffold EP<sub>4</sub> receptor agonist BMP-2 Biology (General) QH301-705.5 Corina Vater Elisabeth Mehnert Henriette Bretschneider Julia Bolte Lisa Findeisen Lucas-Maximilian Matuszewski Stefan Zwingenberger Dose-Dependent Effects of a Novel Selective EP<sub>4</sub> Prostaglandin Receptor Agonist on Treatment of Critical Size Femoral Bone Defects in a Rat Model
description	Difficulties in treating pseudarthrosis and critical bone defects are still evident in physicians’ clinical routines. Bone morphogenetic protein 2 (BMP-2) has shown promising osteoinductive results but also considerable side effects, not unexpected given that it is a morphogen. Thus, the bone regenerative potential of the novel selective, non-morphogenic EP<sub>4</sub> prostaglandin receptor agonist KMN-159 was investigated in this study. Therefore, mineralized collagen type-1 matrices were loaded with different amounts of BMP-2 or KMN-159 and implanted into a 5 mm critical-sized femoral defect in rats. After 12 weeks of observation, micro-computed tomography scans were performed to analyze the newly formed bone volume (BV) and bone mineral density (BMD). Histological analysis was performed to evaluate the degree of defect healing and the number of vessels, osteoclasts, and osteoblasts. Data were evaluated using Kruskal-Wallis followed by Dunn’s post hoc test. As expected, animals treated with BMP-2, the positive control for this model, showed a high amount of newly formed BV as well as bone healing. For KMN-159, a dose-dependent effect on bone regeneration could be observed up to a dose optimum, demonstrating that this non-morphogenic mechanism of action can stimulate bone formation in this model system.
format	article
author	Corina Vater Elisabeth Mehnert Henriette Bretschneider Julia Bolte Lisa Findeisen Lucas-Maximilian Matuszewski Stefan Zwingenberger
author_facet	Corina Vater Elisabeth Mehnert Henriette Bretschneider Julia Bolte Lisa Findeisen Lucas-Maximilian Matuszewski Stefan Zwingenberger
author_sort	Corina Vater
title	Dose-Dependent Effects of a Novel Selective EP<sub>4</sub> Prostaglandin Receptor Agonist on Treatment of Critical Size Femoral Bone Defects in a Rat Model
title_short	Dose-Dependent Effects of a Novel Selective EP<sub>4</sub> Prostaglandin Receptor Agonist on Treatment of Critical Size Femoral Bone Defects in a Rat Model
title_full	Dose-Dependent Effects of a Novel Selective EP<sub>4</sub> Prostaglandin Receptor Agonist on Treatment of Critical Size Femoral Bone Defects in a Rat Model
title_fullStr	Dose-Dependent Effects of a Novel Selective EP<sub>4</sub> Prostaglandin Receptor Agonist on Treatment of Critical Size Femoral Bone Defects in a Rat Model
title_full_unstemmed	Dose-Dependent Effects of a Novel Selective EP<sub>4</sub> Prostaglandin Receptor Agonist on Treatment of Critical Size Femoral Bone Defects in a Rat Model
title_sort	dose-dependent effects of a novel selective ep<sub>4</sub> prostaglandin receptor agonist on treatment of critical size femoral bone defects in a rat model
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/71d9ae15f7874ec19e2ad0652a02c8b8
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Dose-Dependent Effects of a Novel Selective EP<sub>4</sub> Prostaglandin Receptor Agonist on Treatment of Critical Size Femoral Bone Defects in a Rat Model

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