Department of Oral Biology, the Maurice and Gabriela Goldschleger School of Dental Medicine, Tel-Aviv University, Tel-Aviv, Israel. © 2010 John Wiley & Sons A/S
J Periodontal Res. 2010 Dec;45(6):731-40. doi: 10.1111/j.1600-0765.2010.01293.x.
Elevated levels of prostaglandins contribute to periodontal destruction but can impair gingival healing by affecting local fibroblasts. Enamel matrix derivative (EMD) has beneficial effects on supporting and gingival tissues. We showed that prostaglandin E(2) (PGE(2) ) inhibits the proliferation of human gingival fibroblasts (hGFs) and that EMD stimulates it. Prostaglandins and EMD may also affect skin healing by targeting dermal fibroblasts (DFs). Thus, we compared the effects of these two agents on the proliferation of hGFs, human gingival keratinocytes (hGKs) and hDFs.
Cells from healthy human gingiva or skin were treated with PGE(2) and/or EMD, and proliferation was assessed by measuring cell number and DNA synthesis.
In hGFs, PGE(2) (1 μm) inhibited proliferation while EMD stimulated it. When present together, EMD abolished the PGE(2) -induced inhibition. Serum increased (by a factor of 10) the amount of phosphorylated extracellular signal-regulated kinase (p-ERK), PGE(2) reduced it (by 70-80%) and EMD restored it when present with PGE(2). Prostaglandin E(2) stimulated cAMP production in hGFs while serum or EMD did not. Enamel matrix derivative stimulated hDF proliferation, but the inhibitory effect of PGE(2) was milder than with hGFs. When present together, EMD abolished the PGE(2) -induced inhibition. Enamel matrix derivative inhibited the proliferation of primary hGKs, but PGE(2) had no effect. Finally, we found that hDFs contained about five times less prostaglandin EP(2) receptor mRNA than hGFs, while hGKs contained none.
Prostaglandin E(2) inhibits and EMD stimulates hGF proliferation via distinct pathways. The different sensitivities of hDFs and hGKs to PGE(2) can be explained by the levels of EP(2) expression.
前列腺素水平升高可导致牙周破坏，但通过影响局部成纤维细胞，可能会损害牙龈愈合。釉基质衍生物（EMD）对支持和牙龈组织有有益的作用。我们发现前列腺素 E2（PGE2）抑制人牙龈成纤维细胞（hGFs）的增殖，而 EMD 则刺激其增殖。前列腺素和 EMD 也可能通过靶向真皮成纤维细胞（DFs）影响皮肤愈合。因此，我们比较了这两种药物对 hGFs、人牙龈角质形成细胞（hGKs）和 hDFs 增殖的影响。
用 PGE2 和/或 EMD 处理来自健康人牙龈或皮肤的细胞，并通过测量细胞数量和 DNA 合成来评估增殖。
在 hGFs 中，PGE2（1μm）抑制增殖，而 EMD 则刺激其增殖。当同时存在时，EMD 消除了 PGE2 诱导的抑制作用。血清（增加 10 倍）磷酸化细胞外信号调节激酶（p-ERK）的量，PGE2（减少 70-80%），当与 PGE2 一起存在时，EMD 恢复其磷酸化水平。前列腺素 E2 刺激 hGFs 中环磷酸腺苷（cAMP）的产生，而血清或 EMD 则不能。EMD 刺激 hDF 增殖，但 PGE2 的抑制作用比 hGFs 弱。当同时存在时，EMD 消除了 PGE2 诱导的抑制作用。EMD 抑制原代 hGKs 的增殖，但 PGE2 无影响。最后，我们发现 hDFs 中 EP2 受体 mRNA 的含量比 hGFs 低约 5 倍，而 hGKs 中则没有。
前列腺素 E2 通过不同的途径抑制 hGF 增殖，而 EMD 则刺激其增殖。hDFs 和 hGKs 对 PGE2 的敏感性不同，可以用 EP2 表达水平来解释。
