A novel selective prostaglandin-receptor EP4-agonist promotes spinal fusion in rats

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Beitragende

Abstract

A novel EP4 selective agonist (KMN-159) was developed [1] and has been proven that it can act as an osteopromotive factor to repair critical-size femoral bone defects in rats at a dose-dependent manner [2]. Based on its osteopromotive properties, we hypothesized that KMN-159 could also aid in bone formation for spinal fusion. Therefore, the aim of this study was to investigate its spinal fusion effect in a dorsolateral spinal fusion model in rats. This study was performed on 192, 10-week-old male Wistar rats. The rats were randomized into 8 groups (n = 12 per group): 1) SHAM (negative control), 2) MCM (scaffold only), 3) MCM + 20 µg BMP-2 (positive control), 4-8) MCM + 0.2, 2, 20, 200 or 2000 µg KMN-159. A posterolateral intertransverse process spinal fusion at L4 to L5 was performed bilaterally by implanting group dependent scaffolds (see above) or left empty in the SHAM group (protocol no. 25-5131/474/38). Animals were euthanized after 3 weeks and 6 weeks for µCT and biomechanical testing analysis. The results showed that KMN-159 promoted new bone formation in a dose-dependent manner at 3 weeks and 6 weeks as verified by µCT. The biomechanical testing showed that the dose of 20, 200 and 2000 µg KMN-159 groups obtained comparable strength with BMP-2 group, which higher than SHAM, MCM and lower doses of 0.2 and 2 µg KMN-159 groups. In conclusion, KMN-159 could be a potential replacement of BMP-2 as a novel osteopromotive factor for spinal fusion. Acknowledgements: We are grateful to Ulrike Heide, Anna-Maria Placht (assistance with surgeries) as well as Suzanne Manthey & Annett Wenke (histology).

Details

OriginalspracheEnglisch
Seiten (von - bis)112-112
Seitenumfang1
FachzeitschriftOrthopaedic Proceedings
Jahrgang106-B
AusgabenummerSUPP_2
PublikationsstatusVeröffentlicht - 2 Jan. 2024
Peer-Review-StatusNein

(Fach-)Tagung

Titel31st Annual Meeting of the European Orthopaedic Research Society
KurztitelEORS 2023
Veranstaltungsnummer31
Dauer27 - 29 September 2023
BekanntheitsgradInternationale Veranstaltung
OrtPorto Congress Centre – Alfândega
StadtPorto
LandPortugal

Externe IDs

ORCID /0000-0003-2834-8933/work/164618194
ORCID /0000-0002-8854-7726/work/164619276
unpaywall 10.1302/1358-992x.2024.2.112

Schlagworte