TGF-Beta Negatively Regulates the BMP2-Dependent Early Commitment of Periodontal Ligament Cells into Hard Tissue Forming Cells.
TGF-Beta Negatively Regulates the BMP2-Dependent Early Commitment of Periodontal Ligament Cells into Hard Tissue Forming Cells.
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TGF-β对牙周韧带细胞对硬组织形成细胞的早期承诺负面调节。
DOI：
10.1371/journal.pone.0125590
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Murakami S
中科院分区：
文献类型：
--
作者：
Kawahara T;Yamashita M;Ikegami K;Nakamura T;Yanagita M;Yamada S;Kitamura M;Murakami S
转化生长因子β（TGF-β）是一种在许多组织和器官中表达的多功能生长因子。遗传动物模型揭示了 TGF-β 在颅面发育（包括牙齿和牙周组织）中的关键功能。然而，TGF-β在牙周膜（PDL）中的生理功能尚未完全阐明。在这项研究中，我们使用 TGF-β 受体激酶抑制剂 SB431542 检查了 TGF-β 在 PDL 细胞细胞分化中的作用。在存在或不存在各种生长因子（例如骨形态发生蛋白（BMP）-2、TGF-β和成纤维细胞生长因子（FGF）-2）的情况下，在含有或不含有SB431542的钙化诱导培养基中培养小鼠PDL细胞克隆（MPDL22）。 SB431542 显着增强 MPDL22 细胞的 BMP-2 依赖性钙化，并在早期成骨细胞分化过程中加速骨化基因碱性磷酸酶 (ALPase) 和 Runt 相关转录因子 (Runx) 2 的表达。在没有 BMP-2 刺激的情况下，SB431542 不会促进 MPDL22 钙化。 SB431542 延迟了 MPDL22 培养后期的细胞生长速率和胶原蛋白合成。定量逆转录聚合酶链反应分析显示，SB431542处理的MPDL22细胞中TGF-β/BMP信号通路中的负反馈成分Smurf1和Smad6的表达下调。这些结果表明，来自 TGF-β 的内源信号负向调节 PDL 细胞向硬组织形成细胞的早期定型和细胞分化。调节内源性 TGF-β 信号的合成药物可能对开发牙周再生疗法有效。
Transforming growth factor beta (TGF-β) is a multi-functional growth factor expressed in many tissues and organs. Genetic animal models have revealed the critical functions of TGF-β in craniofacial development, including the teeth and periodontal tissue. However, the physiological function of TGF-β in the periodontal ligament (PDL) has not been fully elucidated. In this study, we examined the roles of TGF-β in the cytodifferentiation of PDL cells using a TGF-β receptor kinase inhibitor, SB431542. Mouse PDL cell clones (MPDL22) were cultured in calcification-inducing medium with or without SB431542 in the presence or absence of various growth factors, such as bone morphogenetic protein (BMP)-2, TGF-β and fibroblast growth factor (FGF)-2. SB431542 dramatically enhanced the BMP-2-dependent calcification of MPDL22 cells and accelerated the expression of ossification genes alkaline phosphatase (ALPase) and Runt-related transcription factor (Runx) 2 during early osteoblastic differentiation. SB431542 did not promote MPDL22 calcification without BMP-2 stimulation. The cell growth rate and collagen synthesis during the late stage of MPDL22 culture were retarded by SB431542. Quantitative reverse transcription polymerase chain reaction analysis revealed that the expressions of Smurf1 and Smad6, which are negative feedback components in the TGF-β/BMP signaling pathway, were downregulated in MPDL22 cells with SB431542 treatment. These results suggest that an endogenous signal from TGF-β negatively regulates the early commitment and cytodifferentiation of PDL cells into hard tissue-forming cells. A synthetic drug that regulates endogenous TGF-β signals may be efficacious for developing periodontal regenerative therapies.
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影响因子：
7.3
作者：
Gellibert, FO;Woolven, J;Hartley, D
通讯作者：
Hartley, D
DOI：
10.3181/00379727-80-19661
发表时间：
1952-01-01
影响因子：
--
作者：
DAHL, LK
通讯作者：
DAHL, LK
影响因子：
168.9
作者：
Seo, BM;Miura, M;Shi, ST
通讯作者：
Shi, ST
影响因子：
4.8
作者：
Ebisawa, T;Fukuchi, M;Miyazono, K
通讯作者：
Miyazono, K
影响因子：
--
作者：
Mori, Y;Ishida, W;Varga, J
通讯作者：
Varga, J