TY - JOUR
T1 - Prostacyclin analog promotes human dental pulp cell migration via a matrix metalloproteinase 9–related pathway
AU - Seang, S.
AU - Pavasant, P.
AU - Everts, V.
AU - Limjeerajarus, C.N.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - 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.
AB - 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.
U2 - 10.1016/j.joen.2019.03.020
DO - 10.1016/j.joen.2019.03.020
M3 - Article
C2 - 31109753
SN - 0099-2399
VL - 45
SP - 873
EP - 881
JO - Journal of endodontics
JF - Journal of endodontics
IS - 7
ER -