Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL-induced osteoclastogenesis.
Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL-induced osteoclastogenesis.
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DOI：
10.1096/fj.201700316r
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Su J
中科院分区：
文献类型：
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作者：
Chen X;Zhi X;Pan P;Cui J;Cao L;Weng W;Zhou Q;Wang L;Zhai X;Zhao Q;Hu H;Huang B;Su J
骨质疏松症是一种代谢性骨病，其特征是由于骨蛋白和矿物质含量的过度损失而导致骨密度和强度下降。成骨细胞和破骨细胞之间的不平衡是绝经后骨质疏松的发病机制之一。雌激素停用导致促炎细胞因子水平升高。炎症过度激活的破骨细胞在这种失衡中起着至关重要的作用。苦参碱是一种在苦参属植物中发现的生物碱，具有多种药理作用，包括抗炎活性。本研究表明，苦参碱通过降低血清中TRAcp5b、TNF-α和IL-6的水平，可以显著预防卵巢切除术诱导的骨丢失，并抑制体内破骨细胞的生成。抗酒石酸酸性磷酸酶（TRAP）染色和肌动蛋白环的形成以及骨坑形成实验表明，在体外，苦参碱能显著抑制NF-κB配体受体激活剂（RANKL）和M-CSF诱导的骨髓单核细胞和RAW264.7细胞的破骨细胞分化。在分子机制方面，苦参碱可抑制rankl诱导的NF-κB、AKT和MAPK通路的激活，抑制破骨细胞发生相关标志物的表达，包括基质金属蛋白酶9、NFATc1、TRAP、C-Src和组织蛋白酶k。我们的研究表明，苦参碱通过调节多种途径抑制破骨细胞的发生，在治疗骨质疏松等破骨细胞相关疾病方面具有重要意义。-陈晓明，志新，潘鹏，崔健，曹磊，翁，文，周，强，王，良，翟晓明，赵，强，胡，红，黄，波，苏，杰。苦参碱通过抑制rankl诱导的破骨细胞生成来预防去卵巢小鼠骨质流失。
Osteoporosis is a metabolic bone disease characterized by decreased bone density and strength due to excessive loss of bone protein and mineral content. The imbalance between osteogenesis by osteoblasts and osteoclastogenesis by osteoclasts contributes to the pathogenesis of postmenopausal osteoporosis. Estrogen withdrawal leads to increased levels of proinflammatory cytokines. Overactivated osteoclasts by inflammation play a vital role in the imbalance. Matrine is an alkaloid found in plants from the Sophora genus with various pharmacological effects, including anti-inflammatory activity. Here we demonstrate that matrine significantly prevented ovariectomy-induced bone loss and inhibited osteoclastogenesis in vivo with decreased serum levels of TRAcp5b, TNF-α, and IL-6. In vitro matrine significantly inhibited osteoclast differentiation induced by receptor activator for NF-κB ligand (RANKL) and M-CSF in bone marrow monocytes and RAW264.7 cells as demonstrated by tartrate-resistant acid phosphatase (TRAP) staining and actin-ring formation as well as bone resorption through pit formation assays. For molecular mechanisms, matrine abrogated RANKL-induced activation of NF-κB, AKT, and MAPK pathways and suppressed osteoclastogenesis-related marker expression, including matrix metalloproteinase 9, NFATc1, TRAP, C-Src, and cathepsin K. Our study demonstrates that matrine inhibits osteoclastogenesis through modulation of multiple pathways and that matrine is a promising agent in the treatment of osteoclast-related diseases such as osteoporosis.—Chen, X., Zhi, X., Pan, P., Cui, J., Cao, L., Weng, W., Zhou, Q., Wang, L., Zhai, X. Zhao, Q., Hu, H., Huang, B., Su, J. Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL-induced osteoclastogenesis.