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Prostacyclin Analog Promotes Human Dental Pulp Cell Migration via a Matrix Metalloproteinase 9-related Pathway

Prostacyclin Analog Promotes Human Dental Pulp Cell Migration via a Matrix Metalloproteinase 9-related Pathway

Sonntana Seang, Prasit Pavasant, Vincent Everts, Chalida Nakalekha Limjeerajarus

J Endod. 2019 Jul;45(7):873-881.

PMID: 31109753

Abstract:

Introduction:
During dental pulp healing, progenitor cells migrate to the injured site. This study investigated the effect of iloprost (an exogenous prostacyclin [PGI2]) on enhancing human dental pulp cell (HDPC) migration and its underlying mechanism.
Methods:
HDPC migration was analyzed using a wound scratch assay. HDPCs were obtained from extracted teeth and cultured in the presence of iloprost for 24 and 72 hours. Immunofluorescent staining for matrix metalloproteinase 9 (MMP-9), quantitative polymerase chain reaction gene expression analysis, gelatin zymography, and enzyme-linked immunosorbent assay of MMP-9 expression were performed. A PGI2 (IP) antagonist, protein kinase A (PKA) inhibitor, and MMP-9 inhibitor were used to inhibit the IP receptor, PKA signaling pathway, and MMP-9 activity, respectively.
Results:
A mechanically applied scratch in HDPC cultures closed more rapidly in the presence of iloprost. This result coincided with increased MMP-9 messenger RNA and protein expression and higher gelatinase activity. These iloprost-enhanced effects were inhibited by an IP receptor antagonist or a PKA inhibitor. Forskolin, a PKA activator, increased MMP-9 expression concomitant with increased migration. The application of a selective MMP-9 inhibitor resulted in decreased iloprost-induced migration.
Conclusions:
MMPs play an important role in cell migration by degrading components of the extracellular matrix. In this study, iloprost accelerated HDPC migration in a wound scratch assay. MMP-9 expression was increased concomitantly by iloprost and appeared to be mediated by the IP-PKA pathway. These observations suggest that iloprost may enhance dental pulp tissue healing by up-regulating MMP-9. The PGI2 analog might be a promising biomolecule in dental pulp regenerative treatment.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4241277	MMP-9 human			Price

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