Zhejiang University School of Medicine, Hangzhou, 310009, China.
Department of Orthopedic, Taizhou Hospital of Zhejiang Province, Zhejiang University, No. 150 Ximen Street, Gucheng Street, Linhai City, Taizhou City, 317000, Zhejiang Province, China.
Inflammopharmacology. 2022 Aug;30(4):1445-1458. doi: 10.1007/s10787-022-00985-1. Epub 2022 Apr 22.
As the main cause of osteoporosis, abnormal activity of osteoclasts could disrupt the balance between bone resorption and formation. Moreover, up-regulation of nuclear factor-kappa ligand (RANKL) expression by chronic inflammation-mediated inflammatory factors might contribute to the differentiation of osteoclast precursor cells. Therefore, an anti-inflammatory agent named yangonin was presented for inhibiting osteoclast and relieving inflammatory osteoporosis through down-regulating inflammatory factors.
We established a model of macrophage inflammation and then verified the anti-inflammatory effect of yangonin. The inhibitory effect of yangonin on osteoclasts was detected by tartrate-resistant acid phosphatase (TRAP) staining, Western blotting and quantitative real-time PCR (qRT-PCR). Finally, micro-CT, TRAP and hematoxylin-eosin (HE) staining were used to show the effect of yangonin on inflammatory osteoporosis in vivo.
Our results suggested that yangonin was able to reduce the secretion of inflammatory factors, down-regulate osteoclast-related genes such as TRAP, RANKL, cathepsin K (CTSK) and nuclear factor-activated T-cell 1 (NFATc1). Furthermore, it was demonstrated that yangonin could suppress the function of inflammatory cytokines in osteoclast differentiation and reporting, wherein NF-κB, AKT and downstream c-Fos/NFATc1 signaling pathways were involved. In an in vivo study, we implied that yangonin has a relieving effect on inflammatory osteoporosis.
Our research shows that yangonin down-regulates inflammatory factors and inhibits the bone-breaking effect of inflammation through NF-κB, AKT and downstream c-Fos/NFATc1 signaling pathways to achieve the purpose of treating inflammatory osteoporosis.
破骨细胞的异常活动是骨质疏松症的主要原因，它会破坏骨吸收和形成之间的平衡。此外，慢性炎症介导的炎症因子可上调核因子-κB 配体（RANKL）的表达，从而促进破骨细胞前体细胞的分化。因此，我们提出了一种名为白杨素的抗炎剂，通过下调炎症因子来抑制破骨细胞并缓解炎症性骨质疏松症。
我们建立了一个巨噬细胞炎症模型，然后验证了白杨素的抗炎作用。通过抗酒石酸酸性磷酸酶（TRAP）染色、Western blot 和实时定量 PCR（qRT-PCR）检测白杨素对破骨细胞的抑制作用。最后，通过 micro-CT、TRAP 和苏木精-伊红（HE）染色观察白杨素对体内炎症性骨质疏松症的影响。
我们的结果表明，白杨素能够减少炎症因子的分泌，下调破骨细胞相关基因，如 TRAP、RANKL、组织蛋白酶 K（CTSK）和核因子活化 T 细胞 1（NFATc1）。此外，研究表明，白杨素可以抑制炎症细胞因子在破骨细胞分化和报告中的作用，其中涉及 NF-κB、AKT 和下游 c-Fos/NFATc1 信号通路。在体内研究中，我们表明白杨素有缓解炎症性骨质疏松症的作用。
我们的研究表明，白杨素通过 NF-κB、AKT 和下游 c-Fos/NFATc1 信号通路下调炎症因子，抑制炎症的破骨作用，从而达到治疗炎症性骨质疏松症的目的。
