Lycorine protects cartilage through suppressing the expression of matrix metalloprotenases in rat chondrocytes and in a mouse osteoarthritis model
Lycorine protects cartilage through suppressing the expression of matrix metalloprotenases in rat chondrocytes and in a mouse osteoarthritis model
复制标题
石蒜碱通过抑制大鼠软骨细胞和小鼠骨关节炎模型中基质金属蛋白酶的表达来保护软骨。
DOI：
10.3892/mmr.2016.5594
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发表时间：
2016-10-01
影响因子：
3.4
通讯作者：
Fan, Shun-Wu
中科院分区：
文献类型：
--
作者：
Chen, Shuai;Fang, Xiang-Qian;Fan, Shun-Wu
细胞外基质（ECM）降解酶，包括基质金属蛋白酶（MMPs），在骨关节炎（OA）进展中对软骨破坏至关重要。因此，鉴定抑制MMPs合成的新药可能有助于OA的治疗。石蒜碱的细胞毒性使用CCK 8测定法测定。通过Western blot和逆转录-定量聚合酶链反应检测石蒜碱对IL-1诱导的MMPs上调和丝裂原活化蛋白激酶通路激活的影响。苏木精-伊红染色和番红O染色用于评价石蒜碱在小鼠前交叉韧带横断模型中的作用。在本研究中，据我们所知，石蒜碱（LY）在体外抑制白细胞介素-1（IL-1）诱导的MMP-3和MMP-13的合成。分子生物学分析表明，LY可抑制IL-1刺激引起的c-Jun N-末端激酶（JNK）磷酸化和核因子（NF）-B信号通路的激活。此外，在小鼠前交叉韧带横断模型中的体内实验证实了LY对软骨的保护作用。总之，本研究中获得的数据表明，LY通过抑制JNK和NF-B通路抑制IL-1诱导的MMP-3和MMP-13的表达，这表明LY可用作治疗OA的潜在药物。
Extracellular matrix (ECM) degrading enzymes, including matrix metalloproteinases (MMPs), are critical for cartilage destruction in the progression of osteoarthritis (OA). Thus, identifying novel drugs, which suppress the synthesis of MMPs may facilitate the treatment of OA. The cytotoxicity of lycorine was determined using a CCK8 assay. The effects of lycorine on IL-1-induced upregulation of MMPs and activation of mitogen-activated protein kinase pathways were detected by western blot analysis and reverse transcription-quantitative polymerase chain reaction. Hematoxylin and eosin staining and Safranin O staining were used to evaluate the effect of lycorine in a mouse anterior cruciate ligament transection model. In the present study, it was demonstrated for the first time, to the best of our knowledge, that lycorine (LY) suppressed interleukin-1 (IL-1)-induced synthesis of MMP-3 and MMP-13 in vitro. Molecular analysis revealed that LY abrogated the phosphorylation of c-Jun N-terminal kinase (JNK) and the activation of the nuclear factor (NF)-B signaling pathway caused by IL-1 stimulation. In addition, in vivo experiments in a mouse anterior cruciate ligament transection model confirmed the protective role of LY on cartilage. Taken together, the data obtained in the present study demonstrated that LY suppressed the IL-1-induced expression of MMP-3 and MMP-13 through inhibition of the JNK and NF-B pathways, suggesting that LY may be used as a potential drug for the treatment of OA.