Prostaglandin E2 inhibits mineralization and enhances matrix metalloproteinase-13 in mature cementoblasts mainly via the EP4 pathway.
OBJECTIVE
Prostaglandin E(2) (PGE(2)) is an important factor in the pathogenesis of periodontal disease because of bone resorbing activity and association with attachment loss. PGE(2) and PGE receptor subtypes (EPs) play an important role in modulating bone metabolism via osteoblasts. However, little is known about the effects of PGE(2) on cementoblasts. The aims of this study were to determine the expression of EPs in mature cementoblasts, and to examine the effect of PGE(2) and EPs on their cellular function.


METHODS
Expression of EPs in immortalized mouse cementoblasts (OCCM-30 cells), which were characterized as mature cementoblasts, was determined using reverse transcriptase polymerase chain reaction (RT-PCR). The effects of PGE(2) and EP agonists on mineralization were examined by studying nodule formation with alizarin red S staining. Alkaline phosphatase (ALP) activity with PGE(2) and EP4 agonist was examined using the Bessey-Lowry enzymologic method. Effects of the PGE(2)-EP4 pathway on expression levels of osteocalcin (OCN) and matrix metalloproteinase-13 (MMP-13) mRNA were examined using real-time RT-PCR.


RESULTS
OCCM-30 cells expressed EP1, EP2, EP3 and EP4 mRNA. PGE(2) and EP4 agonist led to downregulation of mineralized nodule formation and ALP activity in OCCM-30 cells. OCN mRNA expression was suppressed and MMP-13 mRNA expression was stimulated via the PGE(2)-EP4 pathway in OCCM-30 cells.


CONCLUSIONS
Cementoblasts may downregulate their mineralization ability and upregulate MMP-13 production through the PGE(2)-EP4 pathway, and may contribute to destruction of connective tissue attachment under inflammatory conditions.
Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan.
Hiroko
H
Oka
Mutsumi
M
Miyauchi
Kiyako
K
Sakamoto
Masae
M
Kitagawa
Kazuyuki
K
Noguchi
Martha J
MJ
Somerman
Takashi
T
Takata
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002461:Cell Line, Transformed; D025021:Cementogenesis / Q000187:drug effects*; D003739:Dental Cementum / Q000187:drug effects* / Q000378:metabolism; D003864:Depression, Chemical; D015232:Dinoprostone / Q000494:pharmacology*; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D058309:Receptors, Prostaglandin E, EP4 Subtype; D020133:Reverse Transcriptase Polymerase Chain Reaction
C545651:Ptger4 protein, mouse; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D053509:Matrix Metalloproteinase 13; D015232:Dinoprostone