Mechanical stretch-induced osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (hJBMMSCs) via inhibition of the NF-κB pathway.
Mechanical stretch-induced osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (hJBMMSCs) via inhibition of the NF-κB pathway.
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通过抑制 NF-κB 通路机械拉伸诱导人颌骨骨髓间充质干细胞 (hJBMMSC) 成骨分化
DOI：
10.1038/s41419-018-0279-5
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发表时间：
2018-02-12
影响因子：
9
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Chen X;Liu Y;Ding W;Shi J;Li S;Liu Y;Wu M;Wang H
严重的咬合不正会导致几种严重的牙齿和身体状况，如消化困难、牙周病和严重的蛀牙。正畸治疗主要用于治疗错牙合畸形。正畸牙受力后，压力侧骨吸收，张力侧骨沉积。成骨细胞被认为是张力侧骨再生的关键成分。然而，其潜在机制仍不清楚。在本研究中，我们主要研究机械牵张如何调节正畸治疗过程中的成骨。从健康成人供体中分离人颌骨骨髓间充质干细胞（hJBMMSCs），并在常规培养基（对照）或成骨培养基（OS）中培养。在OS培养下，hJBMMSCs呈现成骨分化潜能，如通过增加的矿化、增强的钙沉积和成骨标志物（ALP、osterix和Runx）的上调表达所证明的。骨诱导hJBMMSCs成骨与IKK的去磷酸化、IKB α的激活和P65的磷酸化/核积累有关，这些都表明NF-κ B活性受到抑制。在hJBMMSCs中过表达P65，可持续激活NF-κ B，阻止骨向成骨分化。之后，我们应用Flexcell张力系统，该系统可使培养的hJBMMSCs产生机械牵拉，以模拟牙齿移动时的张力。机械拉伸导致ALP活性在处理7天和21天后分别增加3.5倍和钙沉积增加2.4倍。ALP、Run × 2和Osterix的表达水平也显著上调。同时，对OS培养的hJBMMSCs施加机械拉伸也显著促进了OS诱导的成骨。OS和机械牵张均下调NF-κ B活性。通过在hJBMMSCs中过表达P65，OS和机械拉伸均不能诱导其成骨。这些结果表明，与OS诱导一样，在非炎症环境中，机械牵张通过抑制NF-κ B促进hJBMMSCs的成骨。
Severe malocclusion can contribute to several serious dental and physical conditions, such as digestive difficulties, periodontal disease, and severe tooth decay. Orthodontic treatment is mainly used to treat malocclusion. Forces in orthodontic tooth results in bone resorption on the pressure side and bone deposition on the tension side. Osteoblasts have been considered as the key component in bone regeneration on the tension side. However, the underlying mechanisms remain unclear. In this study, we focus on how mechanical stretch regulates the osteogenesis during orthodontic treatment. Human jaw bone marrow mesenchymal stem cells (hJBMMSCs) were isolated from healthy adult donors and cultured in regular medium (control) or osteogenic medium (OS). Under OS culture, hJBMMSCs presented osteogenic differentiation potentials, as evidenced by increased mineralization, enhanced calcium deposition, and upregulated expression of osteogenesis markers (ALP, osterix, and Runx). What’s more, the OS-induced osteogenesis of hJBMMSCs is associated with the dephosphorylation of IKK, activation of IKBα, and phosphorylation/nucleic accumulation of P65, which all indicated the inhibition of NF-κB activity. OverexpressingP65in hJBMMSCs, which could constantly activate NF-κB, prevented the osteogenic differentiation in the OS. After that, we applied the Flexcell tension system, which could cause mechanical stretch on cultured hJBMMSCs to mimic the tension forces during tooth movement. Mechanical stretch resulted in 3.5−fold increase of ALP activity and 2.4–fold increase of calcium deposition after 7 days and 21 days treatment, respectively. The expression levels of ALP, Run×2, and Osterix were also significantly upregulated. In the meantime, applying mechanical stretch on OS-cultured hJBMMSCs also dramatically promoted the OS-induced osteogenesis. Both OS and mechanical stretch downregulated NF-κB activity. By overexpressingP65in hJBMMSCs, neither OS nor mechanical stretch could induce their osteogenesis. These results indicated that, like OS induction, mechanical stretch-facilitated osteogenesis of hJBMMSCs by inhibiting NF-κB in the noninflammatory environments.
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影响因子：
6.2
作者：
Julien, Marion;Khoshniat, Solmaz;Guicheux, Jerome
通讯作者：
Guicheux, Jerome
影响因子：
--
作者：
Lohberger B;Kaltenegger H;Stuendl N;Payer M;Rinner B;Leithner A
通讯作者：
Leithner A
影响因子：
4.1
作者：
Akintoye, Sunday O.;Lam, Thanh;Robey, Pamela G.
通讯作者：
Robey, Pamela G.
影响因子：
2.6
作者：
Mensing N;Gasse H;Hambruch N;Haeger JD;Pfarrer C;Staszyk C
通讯作者：
Staszyk C
影响因子：
4.2
作者：
Alansari, Sarah;Sangsuwon, Chinapa;Alikhani, Mani
通讯作者：
Alikhani, Mani