Monotropein Protects Mesenchymal Stem Cells from Lipopolysaccharide-Induced Impairments and Promotes Fracture Healing in an Ovariectomized Mouse Model
Monotropein Protects Mesenchymal Stem Cells from Lipopolysaccharide-Induced Impairments and Promotes Fracture Healing in an Ovariectomized Mouse Model
复制标题
DOI：
10.1007/s00223-023-01130-y
复制
发表时间：
2023-09
影响因子：
4.2
通讯作者：
Shitian Zhao;Liqiang Guo;Wei-rong Cui;Yong-jian Zhao;Jing Wang;Kanghui Sun;Hong Zhang;Yueli Sun;Dongfeng Zhao;Xiaohui Hu;Ziyun Huang;Sheng Lu;Yongjun Wang;Xinhua Liu;Weian Zhang;Bing Shu
中科院分区：
文献类型：
--
作者：
Shitian Zhao;Liqiang Guo;Wei-rong Cui;Yong-jian Zhao;Jing Wang;Kanghui Sun;Hong Zhang;Yueli Sun;Dongfeng Zhao;Xiaohui Hu;Ziyun Huang;Sheng Lu;Yongjun Wang;Xinhua Liu;Weian Zhang;Bing Shu
麒麟菜苦苷是巴戟天中的有效成分之一，用于治疗多种骨关节疾病。本研究旨在观察独角莲苷在体外对脂多糖处理的骨髓间充质干细胞（bMSC）成骨分化的影响，以及在体内局部应用独角莲苷对去卵巢小鼠骨折愈合的影响。采用脂多糖诱导骨髓间充质干细胞建立炎症模型，并经千金藤素处理。进行分子对接分析以评估麒麟菜苦苷与p65之间的潜在相互作用。在切除卵巢的小鼠中建立胫骨中段的横向骨折，并且使用可注射水凝胶将麒麟豆苷局部应用于骨折部位。千金藤苦素可增强原代骨髓间充质干细胞向软骨成骨细胞分化的能力。此外，在原代骨髓间充质干细胞中，独角莲苷挽救了脂多糖诱导的成骨分化障碍，并抑制了脂多糖诱导的p65磷酸化。对接分析表明，麒麟菜蛋白与p65/14-3-3复合物的结合活性强于NF-κB（p65）的选择性抑制剂DP-005。局部应用独角莲苷部分挽救了卵巢切除小鼠骨痂或愈合胫骨的骨量和生物力学性能下降。在经麒麟菜蛋白处理的卵巢切除小鼠中，2周骨痂中Runx 2、Osterix和胶原I的表达部分恢复。总之，局部应用麒麟菜苷促进卵巢切除小鼠的骨折愈合。抑制p65磷酸化和促进骨髓间充质干细胞成骨可能是其部分作用机制。
Monotropein is one of the active ingredients in Morinda Officinalis, which has been used for the treatment in multiple bone and joint diseases. This study aimed to observe the in vitro effects of Monotropein on osteogenic differentiation of lipopolysaccharide treated bone marrow mesenchymal stem cells (bMSCs), and the in vivo effects of local application of Monotropein on bone fracture healing in ovariectomized mice. Lipopolysaccharide was used to set up the inflammatory model in bMSCs, which were treated by Monotropein. Molecular docking analysis was performed to evaluate the potential interaction between Monotropein and p65. Transverse fractures of middle tibias were established in ovariectomized mice, and Monotropein was locally applied to the fracture site using injectable hydrogel. Monotropein enhanced the ability of primary bMSCs in chondro-osteogenic differentiation. Furthermore, Monotropein rescued lipopolysaccharide-induced osteogenic differentiation impairment and inhibited lipopolysaccharide-induced p65 phosphorylation in primary bMSCs. Docking analysis showed that the binding activity of Monotropein and p65/14-3-3 complex is stronger than the selective inhibitor of NF-κB (p65), DP-005. Local application of Monotropein partially rescued the decreased bone mass and biomechanical properties of callus or healed tibias in ovariectomized mice. The expressions of Runx2, Osterix and Collagen I in the 2-week callus were partially restored in Monotropein-treated ovariectomized mice. Taking together, local application of Monotropein promoted fracture healing in ovariectomized mice. Inhibition of p65 phosphorylation and enhancement in osteogenesis of mesenchymal stem cells could be partial of the effective mechanisms.