齒間乳突的缺失，特別是在前牙區，對於牙科團隊來說是相當大的挑戰。這種情形會造成美觀上的缺陷，發音困難，以及食物塞入牙縫中的困擾並且容易造成牙周方面的問題。而造成這種齒間乳突缺失的原因相當多，且不侷限於其中一種因素，包含了牙周病，或經過牙周治療之後，外傷或是其他醫源性的因素。已經有相當多的文獻發表利用軟、硬組織的移植來解決這種問題，但是因為這個區域的血液供應量有限且會進一步危害到移植組織，使得失敗的風險大大增加。然而有時候我們可以發現到在一些由藥物引發或是遺傳性的牙齦增生通常會先發生在齒間乳突，顯示齒間乳突是有容易增生的傾向。這種特徵有可能是因為齒間乳突具有一些特別的細胞或是分子特性。而在先前的文獻中已經發現到齒間乳突相對於邊緣牙齦具有明顯的特殊分子表現(如keratin 19 ,為表皮幹細胞標記)，也因此我們想要了解是否齒間乳突含有較多的幹細胞，使其在適當的刺激下容易增生，並且齒間乳突這種特殊的細胞及分子組
成是由先天決定或是由後天發育所影響。
對於了解齒間乳突上皮細胞是否特別具有幹細胞的分子表現，我們從健康人類身上取下牙齦組織將其分成兩組(兩相鄰有接觸牙之齒間乳突、邊緣牙齦)，分別針對keratin15、keratin 19、Sox-2、Oct-4、β-catenin、integrinα6、 integrinβ1、 p63 和melanoma chondroitin sulfate proteoglycan。每ㄧ組以免疫組織化學染色來檢測其分子特徵表現。而在染色結果中發現，在兩相鄰有接觸牙之齒間乳突會有某些特殊的分子表現(如:K19、 Sox-2、 β-catenin)，然而Sox-2、 β-catenin的表現在樣本群中並不一致，也因此後續部份主要針對K19來做分析。此外，為了了解主要是由先天基因或是後天環境所調控這種表現，我們更進一步分析兩相鄰無接觸牙之齒間乳突，無齒牙齦以及增生牙齦以釐清之間的關係。從免疫組織化學染色分析中可以發現，K19在兩相鄰無接觸牙之齒間乳突及無齒牙齦的基底細胞層顯得較淡甚至是沒有表現，因此我們推測齒間乳突這種特殊的表現似乎是受牙齒周圍的環境所影響，並且當牙齦增生或是局部發炎時，K19的表現亦會增加。
另外，對於齒間乳突是否含有較多的幹細胞組成，我們分別從邊緣牙齦及齒間乳突取下組織培養在含有bromodeoxyuridine(BrdU)的培養液中， 並追蹤一段時間來標記及比較幹細胞的存在與數量；同樣的，我們也利用母鼠在懷孕中期注射BrdU，並且在幼鼠產下四週後再分析幼鼠齒間乳突及邊緣牙齦的幹細胞含量。從最終的結果中都可以發現，齒間乳突確實含有較多的標記滯留細胞，因此我們可以推測相較於邊緣牙齦，齒間乳突的確是有較多的幹細胞表現。

Loss of the interdental papilla, especially the anterior area, is a significant challenge to the dental team. It can cause esthetic concerns, phonetic difficulties, and food impaction leading to periodontal problems. The reason for tissue loss in the interproximal regions can occur in a variety conditions, including, but not limited to, periodontal diseases, treatment of periodontal diseases, trauma, and other iatrogenic causes. To resolve this problem, lots of papers have presented surgical techniques aimed at grafting hard and soft tissue, but due to limited blood supply and access plague these approaches, significantly increasing the risk for failure. However we can discover drug-induced or hereditary gingival overgrowth, usually starts at the interdental papilla, suggesting that the interdental papilla is predisposed to gingival overgrowth. It is possible that the interdental papilla has unique functional characteristics that are due to distinct cellular or molecular properties, and the strong expression of certain molecules ( Ex: keratin 19 , the skin stem cell marker) at the interdental papilla is reported distinct from marginal gingiva. Therefore we want to know if the interdental papilla contains more stem cells, which make the interdental papilla tend to overgrowth, and this distinct cellular and molecular properties are determined by the congenital or acquired development.
For testing if the interdental papilla expresses the specific markers of stem cells, biopsies of gingival tissue were obtained from healthy human and divided into 2 groups (papilla between two contact teeth、marginal gingival ), then using the immunohistochemistry to check the expressions of keratin15, keratin 19, Sox-2, Oct-4, β-catenin, integrin α6, integrinβ1, p63 and melanoma chondroitin sulfate proteoglycan. In the results of IHC staining, we find the contact interdental papilla expresses some specific molecules ( K19, Sox-2, β-catenin). However, the expressions of Sox-2 and β-catenin are not consistent in the group of interdental papilla. Therefore, in the next part, we focus on analyzing the expressions of K19. To understand the regulation of these genes, we further examined the mucosae from papilla between two open contact teeth, edentulous area and overgrowth gingiva. In the result of IHC analysis, we can find there are no or slight K19 expressions in the group of the papilla between two open contact teeth and edentulous area . Therefore, we suspect anatomical factors play an important role to the expression of K19 at interdental papilla, and the expression of K19 was enhanced when gingiva overgrowth or inflammation.
Besides, for testing if the interdental papilla has more stem cells than marginal gingiva, we cultured the tissues from interdental papilla between two contact teeth and marginal gingiva in the medium contains bromodeoxyuridine (BrdU) then chasing for several weeks to label and compare the stem cells. Similarly, we injected BrdU solution into the pregnant mouse, and after the baby mouse was four weeks old, we analyzed the stem cells between the interdental papilla between two contact teeth and marginal gingiva. In the results of the in vitro and in vivo test, we found there were more BrdU retained cells in the interdental papilla, therefore interdental papilla indeed has more stem cells expressions than marginal gingiva.

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