Rapamycin-Induced Autophagy Promotes the Chondrogenic Differentiation of Synovium-Derived Mesenchymal Stem Cells in the Temporomandibular Joint in Response to IL-1β.
Rapamycin-Induced Autophagy Promotes the Chondrogenic Differentiation of Synovium-Derived Mesenchymal Stem Cells in the Temporomandibular Joint in Response to IL-1β.
复制标题
雷帕霉素诱导的自噬促进颞下颌关节中滑膜来源的间充质干细胞对 IL-1β 的软骨分化
DOI：
10.1155/2020/4035306
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发表时间：
2020
影响因子：
--
通讯作者：
Shao L
中科院分区：
文献类型：
--
作者：
Liu W;Luo H;Wang R;Kang Y;Liao W;Sun Y;Chen G;Shao L
颞下颌关节紊乱病（TMD）的软骨缺损会导致慢性疼痛，而且很少愈合。滑膜间充质干细胞（SMSCs）具有上级软骨形成能力，已成为软骨组织工程的种子细胞。然而，影响SMSCs修复关节软骨的局部炎症状况提出了挑战，并且功能的具体机制仍不清楚。因此，探索SMSCs在TMD炎症条件下的软骨形成是重要的，以便它们可以更有效地用于临床治疗。在这项研究中，我们从患有严重软骨损伤的TMD患者中获得SMSCs。在软骨形成分化过程中，作为TMD中最普遍的细胞因子之一的IL-1β刺激引起MMP 13表达增加，而SOX 9、聚集蛋白聚糖和胶原II表达减少。同时，IL-1β可上调mTOR的表达，降低LC 3-II/LC 3-I比值，减少自噬体的形成。进一步的研究表明，在IL-1β存在的情况下，雷帕霉素预处理可通过诱导自噬促进SMSCs的迁移和软骨形成相关标志物的表达。3-苄基-5-（（2-硝基苯氧基）甲基）-二氢呋喃-2（3 H）-酮（3BDO）是一种新的mTOR激活剂，可抑制自噬，增加p-GSK 3 β ser 9和β-catenin的表达，类似于IL-1β的刺激作用。此外，雷帕霉素可降低mTOR的表达，而GSK 3 β抑制剂TWS 119可阻断mTOR对LC 3-II/LC 3-I的促进作用。综上所述，这些结果表明雷帕霉素通过诱导自噬来增强SMSCs的软骨形成，并且GSK 3 β可能是雷帕霉素诱导自噬过程中的重要调节剂。因此，诱导自噬可能是炎症微环境中SMSCs软骨分化的一种有用方法，并可能代表一种新的TMD治疗方法。
Cartilage defects in temporomandibular disorders (TMD) lead to chronic pain and seldom heal. Synovium-derived mesenchymal stem cells (SMSCs) exhibit superior chondrogenesis and have become promising seed cells for cartilage tissue engineering. However, local inflammatory conditions that affect the repair of articular cartilage by SMSCs present a challenge, and the specific mechanism through which the function remains unclear. Thus, it is important to explore the chondrogenesis of SMSCs under inflammatory conditions of TMD such that they can be used more effectively in clinical treatment. In this study, we obtained SMSCs from TMD patients with severe cartilage injuries. In response to stimulation with IL-1β, which is well known as one of the most prevalent cytokines in TMD, MMP13 expression increased, while that of SOX9, aggrecan, and collagen II decreased during chondrogenic differentiation. At the same time, IL-1β upregulated the expression of mTOR and decreased the ratio of LC3-II/LC3-I and the formation of autophagosomes. Further study revealed that rapamycin pretreatment promoted the migration of SMSCs and the expression of chondrogenesis-related markers in the presence of IL-1β by inducing autophagy. 3-Benzyl-5-((2-nitrophenoxy)methyl)-dihydrofuran-2(3H)-one (3BDO), a new activator of mTOR, inhibited autophagy and increased the expression of p-GSK3βser9 and β-catenin, simulating the effect of IL-1β stimulation. Furthermore, rapamycin reduced the expression of mTOR, whereas the promotion of LC3-II/LC3-I was blocked by the GSK3β inhibitor TWS119. Taken together, these results indicate that rapamycin enhances the chondrogenesis of SMSCs by inducing autophagy, and GSK3β may be an important regulator in the process of rapamycin-induced autophagy. Thus, inducing autophagy may be a useful approach in the chondrogenic differentiation of SMSCs in the inflammatory microenvironment and may represent a novel TMD treatment.
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DOI：
10.1002/ar.23798
发表时间：
2018-07-01
影响因子：
2
作者：
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通讯作者：
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影响因子：
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影响因子：
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