TGF-β in jaw tumor fluids induces RANKL expression in stromal fibroblasts.
TGF-β in jaw tumor fluids induces RANKL expression in stromal fibroblasts.
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DOI：
10.3892/ijo.2016.3548
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发表时间：
2016-08
影响因子：
5.2
通讯作者：
Kogo M
中科院分区：
文献类型：
--
作者：
Yamada C;Aikawa T;Okuno E;Miyagawa K;Amano K;Takahata S;Kimata M;Okura M;Iida S;Kogo M
牙源性肿瘤和囊肿，发生在颌骨，生长的吸收和破坏的颌骨。然而，牙源性肿瘤/囊肿的骨吸收机制尚不清楚。牙源性肿瘤/囊肿包括牙源性上皮细胞和间质成纤维细胞，其起源于发育中的牙胚。已经证明，发育中的牙胚的牙源性上皮细胞诱导破骨细胞生成，以防止牙胚侵入发育中的骨，从而维持其在发育中的骨中的结构。因此，我们假设牙源性肿瘤/囊肿的牙源性上皮细胞诱导破骨细胞形成，这在肿瘤/囊肿长入颌骨中起着潜在的作用。本研究的目的是通过细胞因子来检测破骨细胞的生成，重点是牙源性上皮细胞产生的转化生长因子-β（TGF-β）。我们观察了牙源性角化囊性瘤液诱导NF-κB配体受体激活因子（RANKL）的两条途径：通过白细胞介素-1 α（IL-1α）信号传导的环氧化酶-2（考克斯-2）/前列腺素E2（PGE 2）途径和通过TGF-β受体信号传导的非考克斯-2/PGE 2途径。牙源性肿瘤/囊肿产生的TGF-β1和IL-1α直接在破骨细胞前体细胞中诱导破骨细胞生成，并通过基质中RANKL诱导增加间接诱导破骨细胞生成。
Odontogenic tumors and cysts, arising in the jawbones, grow by resorption and destruction of the jawbones. However, mechanisms underlying bone resorption by odontogenic tumors/cysts remain unclear. Odontogenic tumors/cysts comprise odontogenic epithelial cells and stromal fibroblasts, which originate from the developing tooth germ. It has been demonstrated that odontogenic epithelial cells of the developing tooth germ induce osteoclastogenesis to prevent the tooth germ from invading the developing bone to maintain its structure in developing bones. Thus, we hypothesized that odontogenic epithelial cells of odontogenic tumors/cysts induce osteoclast formation, which plays potential roles in tumor/cyst outgrowth into the jawbone. The purpose of this study was to examine osteoclastogenesis by cytokines, focusing on transforming growth factor-β (TGF-β), produced by odontogenic epithelial cells. We observed two pathways for receptor activator of NF-κB ligand (RANKL) induction by keratocystic odontogenic tumor fluid: the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway through interleukin-1α (IL-1α) signaling and non-COX-2/PGE2 pathway through TGF-β receptor signaling. TGF-β1 and IL-1α produced by odontogenic tumors/cysts induced osteoclastogenesis directly in the osteoclast precursor cells and indirectly via increased RANKL induction in the stroma.