XMU-MP-1 attenuates osteoarthritis via inhibiting cartilage degradation and chondrocyte apoptosis.

XMU-MP-1 attenuates osteoarthritis via inhibiting cartilage degradation and chondrocyte apoptosis.
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XMU-MP-1通过抑制软骨降解和软骨细胞凋亡减轻骨关节炎

DOI:
10.3389/fbioe.2022.998077
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发表时间:
2022
影响因子:
5.7
通讯作者:
Jie, Qiang
Jie, Qiang
中科院分区:
工程技术2区
文献类型:
--
作者:
Hao, Xue;Zhao, Jing;Jia, Liyuan;He, Ting;Wang, Huanbo;Fan, Jing;Yang, Yating;Su, Fei;Lu, Qingda;Zheng, Chao;Yang, Liu;Jie, Qiang

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骨关节炎(OA)是最常见的退行性关节疾病;据报道,它与炎症反应、软骨细胞凋亡和软骨变性有关。XMU-MP-1是一种选择性MST1/2抑制剂,可激活下游效应物YAP,促进细胞生长。在小鼠肠道修复、肝脏修复和再生中显示出优异的效果。然而,XMU-MP-1对OA的影响尚不清楚。在这项研究中,我们研究了XMU-MP-1对白细胞介素-1β (IL-1β)诱导的小鼠软骨细胞炎症的治疗作用和内侧半月板手术(DMM)诱导的OA模型的不稳定性。在软骨细胞中,XMU-MP-1升高基质金属蛋白酶(Mmp3, Mmp13),降低IL-1β诱导的细胞外基质(Col2, Acan)。此外,XMU-MP-1强烈抑制il -1β诱导的软骨细胞凋亡,显著促进软骨细胞增殖。此外,XMU-MP-1对小鼠OA模型具有保护和治疗作用。这些发现表明XMU-MP-1可能对软骨退化具有保护作用,可能是OA的一种新的潜在治疗选择。
Osteoarthritis (OA) is the most prevalent type of degenerative joint disease; it is reported to be associated with inflammatory responses, chondrocyte apoptosis, and cartilage degeneration. XMU-MP-1 is a selective MST1/2 inhibitor which activates the downstream effector YAP and promotes cell growth. It has displayed excellent benefits in mouse intestinal repair, as well as liver repair and regeneration. However, the effects of XMU-MP-1 on OA remain unclear. In this study, we investigated the therapeutic role of XMU-MP-1 on interleukin-1β (IL-1β)-induced inflammation in mice chondrocytes and the destabilization of the medial meniscus surgery (DMM)-induced OA model. In chondrocytes, treatment with XMU-MP-1 elevated the matrix metalloproteinases (Mmp3, Mmp13) and decreased the extracellular matrix (Col2, Acan) induced by IL-1β. Moreover, XMU-MP-1 strongly inhibited IL-1β-induced chondrocyte apoptosis and significantly promoted chondrocyte proliferation. Furthermore, XMU-MP-1 demonstrated a protective and therapeutic influence on the mouse OA model. These findings indicate that XMU-MP-1 may have a protective effect on cartilage degradation and may be a new potential therapeutic option for OA.
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