Bushen huoxue decoction inhibits RANKL-stimulated osteoclastogenesis and glucocorticoid-induced bone loss by modulating the NF-κB, ERK, and JNK signaling pathways.
Bushen huoxue decoction inhibits RANKL-stimulated osteoclastogenesis and glucocorticoid-induced bone loss by modulating the NF-κB, ERK, and JNK signaling pathways.
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补肾活血汤通过调节 NF-κB、ERK 和 JNK 信号通路抑制 RANKL 刺激的破骨细胞生成和糖皮质激素诱导的骨丢失
DOI：
10.3389/fphar.2022.1007839
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发表时间：
2022
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
糖皮质激素诱导的骨质疏松症（GIOP）是继发性骨质疏松症的最常见形式，其由破骨细胞过度活化引起的骨代谢紊乱引起。补肾活血汤是一种具有抗炎、抗氧化、促进干细胞迁移等多种药理作用的中药复方。然而，BHD对破骨细胞生成的影响尚未报道。在这项研究中，我们旨在阐明BHD对RANKL刺激的破骨细胞生成的影响，并探讨其体外作用的潜在机制。我们的研究结果表明，BHD对BMP和RAW264.7细胞的活力没有影响，但抑制RANKL诱导的破骨细胞的形成。此外，补阳还可减弱RANKL诱导的NF-κB、ERK和JNK信号传导。NF-κB、ERK和JNK活化的减弱足以阻碍下游c-fos和NFATc 1及相关特异性基因的表达。同时观察补阳还五汤对糖皮质激素性骨质疏松小鼠的治疗作用。结果表明，补阳还五汤通过抑制破骨细胞活性，预防糖皮质激素诱导的骨质疏松，并保持骨量。总的来说，BHD显示出显著的破骨细胞抑制作用，在骨质疏松症的治疗中具有很大的前景。
Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis, which is caused by a disorder in bone metabolism due to excessive activation of osteoclasts. Bushen Huoxue decoction (BHD) is an herbal formula with multiple pharmacological effects, including anti-inflammatory, antioxidant activity and stem cell migration promotion. However, the effect of BHD on osteoclastogenesis has not been reported. In this study, we aimed to elucidate the effect of BHD on RANKL-stimulated osteoclastogenesis and explored its underlying mechanisms of action in vitro. Our results show that BHD had no effect on BMMs and RAW264.7 cells viability, but inhibited RANKL-induced osteoclast formation in vitro. Furthermore, BHD attenuated RANKL-induced NF-κB, ERK, and JNK signaling. The attenuation of NF-κB, ERK, and JNK activation were enough to impede downstream expression of c-fos and NFATc1 and related specific genes. Meanwhile, we investigated the therapeutic effect of BHD on glucocorticoid-induced osteoporosis (GIOP) mice. The result indicated that BHD prevents glucocorticoid-induced osteoporosis and preserves bone volume by repressing osteoclast activity. Collectively, BHD shows significant osteoclast inhibition and holds great promise in the treatment of osteoporosis.
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影响因子：
4.1
作者：
Ito, Shinsuke;Suzuki, Naoto;Takagi, Minoru
通讯作者：
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影响因子：
5
作者：
den Uyl, Debby;Bultink, Irene E. M.;Lems, Willem F.
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Lems, Willem F.
影响因子：
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作者：
Liu, Shi-Yi;Meng, Xiang-Fei;Zhang, Ning
通讯作者：
Zhang, Ning
影响因子：
6.2
作者：
Cappariello, Alfredo;Loftus, Alexander;Teti, Anna
通讯作者：
Teti, Anna