Fructus Ligustri Lucidi preserves bone quality through induction of canonical Wnt/β-catenin signaling pathway in ovariectomized rats
Fructus Ligustri Lucidi preserves bone quality through induction of canonical Wnt/β-catenin signaling pathway in ovariectomized rats
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女贞子通过诱导卵巢切除大鼠的经典 Wnt/β-catenin 信号通路来保持骨质量
DOI：
10.1002/ptr.6817
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发表时间：
2020-08-04
影响因子：
7.2
通讯作者：
Pei, Xiaohua
中科院分区：
文献类型：
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作者：
Liu, Haixia;Guo, Yubo;Pei, Xiaohua
女贞子（Fructus Ligustri Lucidi，FLL）在临床前和临床上均用于治疗肌肉骨骼疾病。然而，在骨质疏松症的管理中，FLL是否以及如何影响经典的Wnt/β-连环蛋白信号传导仍然是未知的。为此，卵巢切除（OVX）大鼠和原代成骨细胞分别给予FLL水提取物和含药血清。补充FLL对OVX大鼠通过减轻骨密度、强度和微观结构的降低来维持骨质量。这种维持可能与大鼠股骨和胫骨中胰岛素样生长因子-1、骨保护素、磷酸（p）-低密度脂蛋白受体相关蛋白6、p-糖原合成酶激酶3 β（GSK 3 β）、β-连环蛋白、Runx 2和c-Myc的表达上调以及硬化素（SOST）、dickkopf相关蛋白1（DKK 1）、GSK 3 β和p-β-连环蛋白的表达下调有关。此外，含药血清通过抑制DKK 1和SOST过表达激活Wnt/β-连环蛋白信号传导促进成骨细胞骨形成。红景天苷可能是FLL中有益于骨稳态的活性成分之一。总之，我们的研究结果表明，FLL可以通过抑制DKK 1和SOST过表达诱导经典Wnt/β-连环蛋白信号传导来保持骨质量。FLL可能为DKK 1或SOST抑制剂提供新的抗骨质疏松剂来源。
Fructus Ligustri Lucidi(FLL) has been preclinically and clinically used to treat musculoskeletal diseases. However, whether and how FLL affect the canonical Wnt/beta-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 (GSK3 beta), beta-catenin, Runx2 and c-Myc, and downregulating the expressions of sclerostin (SOST), dickkopf-related protein 1 (DKK1), GSK3 beta and p-beta-catenin in rat femurs and tibias. In addition, the medicated serum promotes osteoblastic bone formation through activation of Wnt/beta-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/beta-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.