Human dental follicle cells acquire cementoblast features under stimulation by BMP-2/-7 and enamel matrix derivatives (EMD) in vitro
Human dental follicle cells acquire cementoblast features under stimulation by BMP-2/-7 and enamel matrix derivatives (EMD) in vitro
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DOI：
10.1007/s00441-007-0397-3
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发表时间：
2007-08-01
影响因子：
3.6
通讯作者：
Salles, Jean-Pierre
中科院分区：
文献类型：
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作者：
Kemoun, Philippe;Laurencin-Dalicieux, Sara;Salles, Jean-Pierre
牙囊（DF）是一种外胚间充质组织，由来自颅神经嵴的各种细胞群组成。人牙囊细胞（HDFC）被认为含有成牙骨质细胞、牙周膜细胞和成骨细胞的前体细胞。由Hertwig上皮根鞘产生或存在于釉质基质衍生物（EMD）中的骨形态发生蛋白（BMPs）似乎参与DF细胞分化的控制，但它们的精确功能在很大程度上仍然未知。我们报告了STRO-1（多能间充质祖细胞的标志物）和BMP受体（BMPR）在体内DF中的免疫定位。在培养中，HDFC共表达STRO-1/BMPR，并表现出多谱系特性。与rhBMP-2和rhBMP-7或EMD孵育24 h可增加HDFC表达BMP-2和BMP-7。rhBMP-2和/或rhBMP-7或EMD对这些细胞的长期刺激显著增加碱性磷酸酶活性（AP）和矿化。牙骨质附着蛋白（CAP）和牙骨质蛋白-23（CP-23），两个假定的成牙骨质细胞标志物的表达，已被检测到在EMD刺激的整个DF和培养的HDFC刺激EMD或BMP-2和BMP-7。rhNoggin是一种BMP拮抗剂，可消除HDFC培养物中的AP活性、矿化和CAP/CP-23表达以及EMD诱导的BMP-2和BMP-7表达。Smad-1和MAPK的磷酸化被EMD或rhBMP-2刺激。然而，在这些条件下，rhNoggin仅阻断Smad-1磷酸化。因此，EMD可以激活HDFC向成牙骨质细胞表型，主要（但不限于）涉及外源性和内源性BMP依赖性途径的影响。
The dental follicle (DF) surrounding the developing tooth germ is an ectomesenchymal tissue composed of various cell populations derived from the cranial neural crest. Human dental follicle cells (HDFC) are believed to contain precursor cells for cementoblasts, periodontal ligament cells, and osteoblasts. Bone morphogenetic proteins (BMPs) produced by Hertwig's epithelial root sheath or present in enamel matrix derivatives (EMD) seem to be involved in the control of DF cell differentiation, but their precise function remains largely unknown. We report the immunolocalization of STRO-1 (a marker of multipotential mesenchymal progenitor cells) and BMP receptors (BMPR) in DF in vivo. In culture, HDFC co-express STRO-1/BMPR and exhibit multilineage properties. Incubation with rhBMP-2 and rhBMP-7 or EMD for 24 h increases the expression of BMP-2 and BMP-7 by HDFC. Long-term stimulation of these cells by rhBMP-2 and/or rhBMP-7 or EMD significantly increases alkaline phosphatase activity (AP) and mineralization. Expression of cementum attachment protein (CAP) and cementum protein-23 (CP-23), two putative cementoblast markers, has been detected in EMD-stimulated whole DF and in cultured HDFC stimulated with EMD or BMP-2 and BMP-7. RhNoggin, a BMP antagonist, abolishes AP activity, mineralization, and CAP/CP-23 expression in HDFC cultures and the expression of BMP-2 and BMP-7 induced by EMD. Phosphorylation of Smad-1 and MAPK is stimulated by EMD or rhBMP-2. However, rhNoggin blocks only Smad-1 phosphorylation under these conditions. Thus, EMD may activate HDFC toward the cementoblastic phenotype, an effect mainly (but not exclusively) involving both exogenous and endogenous BMP-dependent pathways.