Ethyl caffeate inhibits macrophage polarization via SIRT1/NF-xB to attenuate traumatic heterotopic ossification in mice
Ethyl caffeate inhibits macrophage polarization via SIRT1/NF-xB to attenuate traumatic heterotopic ossification in mice
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DOI：
10.1016/j.biopha.2023.114508
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发表时间：
2023-03-14
影响因子：
7.5
通讯作者：
Liu，Qian
中科院分区：
文献类型：
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作者：
Wang，Hui;Song，Dezhi;Liu，Qian
异位骨化(HO)是指在软组织或关节周围出现成熟的骨组织。炎症是创伤性HO的关键驱动力，巨噬细胞在这一过程中起着重要作用。咖啡酸乙酯(ECF)是矮牵牛中发现的一种关键活性化合物，具有显著的抗炎作用。在此，我们通过切断跟腱和背部烧伤建立了HO小鼠模型，发现HO早期有大量的巨噬细胞浸润，并随着时间的推移而减少。体外和体内实验表明，ECF抑制巨噬细胞极化，机制研究表明它抑制SIRT1/NF-κB信号通路，从而抑制下游炎症细胞因子的释放。体外研究表明，ECF不直接影响间充质干细胞(MSCs)的矿化或成骨分化，但通过降低条件培养液(CM)中炎性细胞因子的水平来抑制这些过程。因此，M1巨噬细胞可能在HO的发病机制中发挥关键作用，而ECF是预防创伤性HO的潜在候选细胞。数据可用性数据将按要求提供
Heterotopic ossification (HO) denotes the presence of mature bone tissue in soft tissues or around joints. Inflammation is a key driver of traumatic HO, and macrophages play an important role in this process. Ethyl caffeate (ECF), a critical active compound found in Petunia, exerts significant anti-inflammatory effects. Herein, we established a mouse model of HO by transection of the Achilles tendon and back burn and found abundant macrophage infiltration in the early stage of HO, which decreased with time.In vitroandin vivoexperiments indicated that ECF inhibited macrophage polarization, and mechanistic studies showed that it inhibited the SIRT1/NF-κB signalling pathway, thereby suppressing the release of downstream inflammatory cytokines. ECF reduced HO in mice, and its effect was comparable to indomethacin (INDO).In vitrostudies revealed that ECF did not directly affect the mineralization of mesenchymal stem cells (MSCs) or osteogenic differentiation but inhibited these processes by reducing the level of inflammatory cytokines in the conditioned medium (CM). Thus, M1 macrophages may play a crucial role in the pathogenesis of HO, and ECF is a prospective candidate for the prevention of trauma-induced HO.Data availabilityData will be made available on request