Elucidation of roles and functions of cementoblasts in the destruction and regeneration of periodontal tissue

在本研究中，我们研究了小鼠牙骨质母细胞系OC-CM 30细胞是否受到白介素1α或来自假单胞菌的脂多糖的刺激。牙周炎和放线杆菌(A.)伴生放线菌产生COX-2依赖的前列腺素E_2，以及产生的前列腺素E_2是否影响IL-1α诱导的IL-6的产生。牙龈假单胞菌和伴生放线菌产生的IL-1、α和内毒素均可诱导前列腺素E_2的产生，且呈时间依赖性。吲哚美辛(COX-1/-2抑制剂)和NS-398(COX-2抑制剂)可完全抑制IL-1、α和脂多糖诱导的PGE2的产生。17-苯基-ω-Trinor PGE_2(EP_1激动剂)和ONO-AE_1-329(EP_4激动剂)模拟PGE_2对牙龈假单胞菌和伴生放线菌诱导OC-CM 30细胞产生IL-6的IL-1、α-和LPS的促进作用。此外，我们还研究了前列腺素E_2对RANKL和OPG表达的影响。PGE_2不能促进RANKL和OPG蛋白的表达。这些结果表明，在OC-CM 30细胞中，牙龈假单胞菌和伴生放线菌的IL-1α和脂多糖以COX-2依赖的方式诱导PG_2的产生，而COX-2衍生的前列腺素E_2通过EP_1和/或EP_4受体上调牙龈假单胞菌和伴生放线杆菌的IL-1α和内毒素的产生。成牙骨质细胞产生的PGE2和IL-6可能参与了牙周病的发病过程。

In the present study, we investigated whether a mouse cementoblast cell line, OC-CM 30 cells, stimulated with interleukin(IL)-1α or lipopolysaccharides (LPS) from Prophyomonas(P.) gingivalis and Actinobacillus(A.) actinomycetemcomitans produced COX-2-dependent PGE_2 and furthermore whether the produced PGE_2 affected IL-1α-induced IL-6 production. IL-1α and LPS from P.gingivalis and A.actinomycetemcomitans time-dependently induced PGE_2 production. Indomethacin (a COX-1/-2 inhibitor) and NS-398 (a COX-2 inhibitor) completely inhibited IL-1 α-and LPS-induced PGE_2 production. 17-phenyl-ω-trinor PGE_2 (an EP_1 agonist) and ONO-AE1-329 (an EP_4 agonist) mimicked PGE_2 enhancement of IL-1α-and LPS from P.gingivalis and A.actinomycetemcomitans induced IL-6 production in OC-CM 30 cells. Furthermore, we investgated the effect of PGE_2 on RANKL and OPG expression. PGE_2 did not enhance RANKL and OPG prtotein expression. From these data, we suggest that in OC-CM 30 cells IL-1α and LPS from P.gingivalis and A.actinomycetemcomitans induced PG_2 production in a COX-2-dependent manner and that the COX-2-derived PGE_2 up-regulates IL-1α-and LPS from P.gingivalis and A.actinomycetemcomitans elicited IL-6 production via EP_1 and/or EP_4 receptors. PGE_2 and IL-6 produced by cementoblasts may be involved in the pathogenesis of periodontal disease.