The Protective Effects of Salubrinal on the Cartilage and Subchondral Bone of the Temporomandibular Joint under Various Compressive Mechanical Stimulations.
The Protective Effects of Salubrinal on the Cartilage and Subchondral Bone of the Temporomandibular Joint under Various Compressive Mechanical Stimulations.
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Salubrinal在各种压缩机械刺激下对颞下颌关节软骨和软骨下骨的保护作用
DOI：
10.1371/journal.pone.0155514
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Wen J;Jiang Y;Zhang C;Chen S;Li H
颞下颌关节（TMJ）上的过度机械负荷可导致下颌软骨退化和软骨下骨侵蚀，但这些条件的治疗仍然具有挑战性。Salubrinal靶向真核生物翻译起始因子2 α，已被证明对骨骼组织具有多种有益作用。在这里，我们研究的影响Salubrinal注射对下颌骨软骨和软骨下骨的TMJ在不同的压缩应力。我们进行了在体内分析，在大鼠模型中使用不同的压缩应力（40 g和80 g），我们观察了时间相关的变性和病理变化，软骨和软骨下骨的TMJ在第1，3和7天，通过组织学测量，亚细胞观察，增殖和凋亡的变化。注射Salubrinal后，软骨厚度恢复，病理改变减轻。在Salubrinal/光（Sal/光）压缩应力组中，药物在第1天最显著地改变了软骨细胞的增殖和凋亡。在Salubrinal/重（Sal/重）压缩应力组中，药物在第1天最显著地增加软骨细胞的增殖，并且在第7天最显著地减少软骨细胞的凋亡。Salubrinal还增加了骨小梁的面积，抑制了TMJ软骨下骨的炎症反应和病理变化。总之，这些结果表明，在各种压缩机械应力下，Salubrinal给药在第1、3和7天不同程度地减少了细胞凋亡并增强了软骨细胞的增殖，这两者都有助于软骨厚度的恢复和病理变化的缓解。Salubrinal还抑制TMJ软骨下骨的炎症反应和病理变化。
Excessive mechanical loads on the temporomandibular joint (TMJ) can cause mandibular cartilage degradation and subchondral bone erosion, but the treatment of these conditions remains challenging. Salubrinal, which target eukaryotic translation initiation factor 2 alpha, has been shown to have multiple beneficial effects on skeletal tissue. Here, we examined the effect of a Salubrinal injection on the mandibular cartilage and subchondral bone of the TMJ under various compressive stresses. We conducted in vivo analyses in rat models using various compressive stresses (40 g and 80 g), and we observed time-related degeneration and pathological changes in the cartilage and subchondral bone of the TMJ at days 1, 3 and 7 through histological measurements, subcellular observation, and changes in proliferation and apoptosis. After the Salubrinal injection, the thickness of the cartilage recovered, and the pathological change was alleviated. In the Salubrinal/light (Sal/light) compressive stress group, the drug altered the proliferation and apoptosis of chondrocytes most significantly at day 1. In the Salubrinal/heavy (Sal/heavy) compressive stress group, the drug increased the proliferation of chondrocytes most significantly at day 1 and reduced the apoptosis of chondrocytes most significantly at day 7. Salubrinal also increased the area of the bone trabeculae and suppressed inflammatory responses and pathological change in the subchondral bone of the TMJ. Together, these results indicate that the administration of Salubrinal reduces apoptosis and strengthens the proliferation of chondrocyte to varying degrees at days 1, 3 and 7 under various compressive mechanical stresses, both of which contribute to the recovery of cartilage thickness and the alleviation of pathological change. Salubrinal also suppresses inflammatory responses and pathological change in the subchondral bone of the TMJ.