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首页> 外文期刊>Life sciences >A novel small molecule, NecroX-7, inhibits osteoclast differentiation by suppressing NF-κB activity and c-Fos expression
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A novel small molecule, NecroX-7, inhibits osteoclast differentiation by suppressing NF-κB activity and c-Fos expression

机译：新型小分子NecroX-7通过抑制NF-κB活性和c-Fos表达抑制破骨细胞分化

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Aims: Osteoclasts, the unique bone-resorbing polykaryons, are responsible for many bone-destructive diseases, such as osteoporosis and rheumatoid arthritis. Hence, the regulation of osteoclast formation is considered a potential therapeutic approach for these diseases. In this study, we investigated the effect of a novel small compound, C 25H 32N 4O 4S 2 (NecroX-7) on osteoclast formation. Main methods: We analyzed the effects of NecoX-7 on receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast differentiation in vitro and LPS-induced bone loss in vivo. Key findings: We observed that NecroX-7 suppressed osteoclast formation from primary bone marrow macrophages (BMMs) in a dose-dependent manner. NecroX-7 significantly inhibited the NF-κB signaling pathway without affecting the activation of the mitogen-activated protein kinases (MAPKs) JNK, p38, and ERK in response to RANKL. In addition, NecroX-7 strongly attenuated the induction of c-Fos and nuclear factor of activated T cells c1 (NFATc1), which are crucial transcription factors for osteoclast differentiation. Mirroring the down-regulation of c-Fos and NFATc1, the expression of osteoclastogenic markers, such as tartrate-resistant acid phosphatase (TRAP) and cathepsin K, was also reduced by the addition of NecroX-7. Furthermore, confirming the in vitro anti-osteoclastogenic effect, NecroX-7 inhibited lipopolysaccharide (LPS)-induced bone loss in vivo. Significance: Our data imply that NecroX-7 is useful as a therapeutic drug for the treatment of bone resorption-associated diseases.
机译：目的：破骨细胞是独特的骨吸收多核体，可导致许多骨破坏性疾病，例如骨质疏松症和类风湿性关节炎。因此，破骨细胞形成的调节被认为是这些疾病的潜在治疗方法。在这项研究中，我们研究了新型小化合物C 25H 32N 4O 4S 2（NecroX-7）对破骨细胞形成的影响。主要方法：我们分析了NecoX-7对核因子κB配体（RANKL）诱导的破骨细胞分化的受体激活剂和LPS诱导的体内骨丢失的影响。主要发现：我们观察到NecroX-7以剂量依赖性方式抑制了原代骨髓巨噬细胞（BMM）的破骨细胞形成。 NecroX-7可以显着抑制NF-κB信号通路，而不会影响响应RANKL的丝裂原活化蛋白激酶（MAPK）JNK，p38和ERK的激活。此外，NecroX-7大大减弱了c-Fos的诱导和活化T细胞c1（NFATc1）的核因子，这是破骨细胞分化的关键转录因子。反映了c-Fos和NFATc1的下调，通过添加NecroX-7也减少了破骨细胞生成标志物（如抗酒石酸的酸性磷酸酶（TRAP）和组织蛋白酶K）的表达。此外，证实了体外抗破骨细胞作用，NecroX-7在体内抑制脂多糖（LPS）诱导的骨丢失。启示：我们的数据表明NecroX-7可用作治疗与骨吸收相关疾病的治疗药物。

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