Ha Hyunil, Shim Ki-Shuk, Ma Jin Yeul
Clinical Research Division, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea.
Korean Medicine Application Center, Korea Institute of Oriental Medicine, Dong-gu, Daegu 701-300, Republic of Korea.
Integr Med Res. 2017 Dec;6(4):434-442. doi: 10.1016/j.imr.2017.09.004. Epub 2017 Sep 20.
The hooks and stems of have been used to mitigate cardiovascular and central nervous system disorders in Asia traditional medicine. Regulation of osteoclast differentiation and activity is a major target for preventing and treating pathological bone diseases.
Tartrate-resistant acid phosphatase (TRAP) activity and the number of TRAP-stained multinucleated cells were used to examine receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. The activation of RANKL-induced signaling pathways and the expression of transcription factors were investigated by western blot analysis and quantitative real-time polymerase chain reaction. The bone resorption activity of osteoclast was studied using a plate coated with hydroxyl-apatite. Trabecular bone destruction was investigated using a RANKL-induced trabecular bone loss mouse model.
We found that water extract of the hooks and stems of (WEUS) inhibits RANKL-induced differentiation of murine bone marrow macrophages and RAW264.7 cells into osteoclasts. WEUS inhibited the activation of NF-κB and the expression of nuclear factor of activated T-cells, cytoplasmic 1. In addition, WEUS suppressed the bone resorbing activity of mature osteoclasts without affecting their survival. Furthermore, oral administration of WEUS suppressed RANKL-induced bone loss with a significant amelioration of trabecular bone micro-structures. WEUS also reduced RANKL-induced increase in serum TRAP5b activity and C-terminal cross-linked telopeptide of type I collagen levels.
The present study demonstrates that WEUS has a pharmacological activity that inhibits osteoclast-mediated bone destruction by suppressing osteoclast differentiation and function. These results suggest that could be a promising herbal candidate for preventing and treating bone diseases such as osteoporosis.
在亚洲传统医学中，[植物名称]的钩和茎已被用于缓解心血管和中枢神经系统疾病。调节破骨细胞的分化和活性是预防和治疗病理性骨疾病的主要靶点。
采用抗酒石酸酸性磷酸酶（TRAP）活性和TRAP染色的多核细胞数量来检测核因子κB受体激活剂配体（RANKL）诱导的破骨细胞分化。通过蛋白质免疫印迹分析和定量实时聚合酶链反应研究RANKL诱导的信号通路激活和转录因子表达。使用涂有羟基磷灰石的平板研究破骨细胞的骨吸收活性。使用RANKL诱导的小梁骨丢失小鼠模型研究小梁骨破坏情况。
我们发现[植物名称]钩和茎的水提取物（WEUS）可抑制RANKL诱导的小鼠骨髓巨噬细胞和RAW264.7细胞分化为破骨细胞。WEUS抑制NF-κB的激活以及活化T细胞核因子细胞质1的表达。此外，WEUS抑制成熟破骨细胞的骨吸收活性，而不影响其存活。此外，口服WEUS可抑制RANKL诱导的骨丢失，并显著改善小梁骨微结构。WEUS还降低了RANKL诱导的血清TRAP5b活性升高和I型胶原C端交联肽水平。
本研究表明，WEUS具有通过抑制破骨细胞分化和功能来抑制破骨细胞介导的骨破坏的药理活性。这些结果表明，[植物名称]可能是预防和治疗骨质疏松症等骨疾病的有前景的草药候选物。
