Diabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, China.
Department of Histology and Embryology, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing, China.
Phytother Res. 2021 Jan;35(1):424-441. doi: 10.1002/ptr.6817. Epub 2020 Aug 4.
Fructus Ligustri Lucidi (FLL) has been preclinically and clinically used to treat musculoskeletal diseases. However, whether and how FLL affect the canonical Wnt/β-catenin signaling in the management of osteoporosis remains largely unknown. To this end, ovariectomized (OVX) rats and primary osteoblasts were administrated with FLL aqueous extract and medicated serum, respectively. Supplement of FLL to OVX rats maintains bone quality by attenuating the reduction in bone mineral density, strength and microstructure. The maintenance may be associated with upregulating the expression of insulin-like growth factor-1, osteoprotegerin, phospho (p)-low-density lipoprotein receptor-related protein 6, p-glycogen synthase kinase 3 beta (GSK3β), β-catenin, Runx2 and c-Myc, and downregulating the expressions of sclerostin (SOST), dickkopf-related protein 1 (DKK1), GSK3β and p-β-catenin in rat femurs and tibias. In addition, the medicated serum promotes osteoblastic bone formation through activation of Wnt/β-catenin signaling via inhibition of DKK1 and SOST overexpression. Salidroside may be one of the active ingredients in FLL that are beneficial for bone homeostasis. In summary, our results suggest that FLL may preserve bone quality through induction of canonical Wnt/β-catenin signaling via inhibition of DKK1 and SOST overexpression. And FLL may offer a new source of the DKK1 or SOST inhibitors in protection against osteoporosis.
女贞子(FLL)已在临床前和临床上用于治疗肌肉骨骼疾病。然而,FLL 是否以及如何影响骨质疏松症管理中的经典 Wnt/β-连环蛋白信号通路在很大程度上尚不清楚。为此,分别给予去卵巢(OVX)大鼠和原代成骨细胞 FLL 水提物和含药血清。向 OVX 大鼠补充 FLL 通过减轻骨密度、强度和微结构减少来维持骨质量。这种维持可能与上调胰岛素样生长因子-1、骨保护素、磷酸化(p)-低密度脂蛋白受体相关蛋白 6、p-糖原合酶激酶 3β(GSK3β)、β-连环蛋白、Runx2 和 c-Myc 的表达以及下调大鼠股骨和胫骨中骨硬化素(SOST)、Dickkopf 相关蛋白 1(DKK1)、GSK3β 和 p-β-连环蛋白的表达有关。此外,含药血清通过抑制 DKK1 和 SOST 过表达激活 Wnt/β-连环蛋白信号通路促进成骨细胞成骨。红景天苷可能是 FLL 中有益于骨稳态的一种活性成分。总之,我们的研究结果表明,FLL 可能通过抑制 DKK1 和 SOST 过表达诱导经典 Wnt/β-连环蛋白信号通路来维持骨质量。并且 FLL 可能为骨质疏松症防治提供新的 DKK1 或 SOST 抑制剂来源。