Chondroprotective Effects and Mechanisms of Dextromethorphan: Repurposing Antitussive Medication for Osteoarthritis Treatment.
Chondroprotective Effects and Mechanisms of Dextromethorphan: Repurposing Antitussive Medication for Osteoarthritis Treatment.
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DOI：
10.3390/ijms19030825
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发表时间：
2018-03-12
影响因子：
5.6
通讯作者：
Ho LJ
中科院分区：
文献类型：
--
作者：
Chen LW;Liu FC;Hung LF;Huang CY;Lien SB;Lin LC;Lai JH;Ho LJ
骨关节炎（OA）是最常见的关节疾病，主要影响老年人。理想的抗OA药物应该具有适度的抗炎作用，并且长期使用时只有有限的毒性或没有毒性。由于止咳药美沙芬（DXM）在动脉粥样硬化和神经系统疾病中具有保护作用，这是老年人中的两种常见疾病，因此我们在本研究中研究了DXM是否可以在促炎性尼古丁刺激的软骨细胞和胶原诱导的关节炎（CIA）动物模型中具有保护作用。从取自猪或OA患者的软骨标本制备软骨细胞。采用Western blotting、定量PCR和免疫组化方法检测Ⅱ型胶原（Col Ⅱ）和基质金属蛋白酶（MMP）的表达。DXM显著恢复了肿瘤坏死因子-α（TNF-α）介导的II型胶原减少，并降低了TNF-α诱导的MMP-13产生。为了抑制MMP-13的合成，DXM阻断TNF-α下游信号传导，包括I κ B激酶（IKK）α/β-IκBα-核因子-κ B（NF-κB）和c-Jun N-末端激酶（JNK）-激活蛋白-1（AP-1）的激活。除此之外，DXM保护CIA小鼠免受严重炎症和软骨破坏。DXM似乎可以保护软骨免受炎症介导的基质降解，这是骨关节炎疾病进展中的不可逆状态。结果表明，测试DXM作为骨关节炎治疗应该是进一步研究的重点。
Osteoarthritis (OA) is the most common joint disorder and primarily affects older people. The ideal anti-OA drug should have a modest anti-inflammatory effect and only limited or no toxicity for long-term use. Because the antitussive medication dextromethorphan (DXM) is protective in atherosclerosis and neurological diseases, two common disorders in aged people, we examined whether DXM can be protective in pro-inflammatory cytokine-stimulated chondrocytes and in a collagen-induced arthritis (CIA) animal model in this study. Chondrocytes were prepared from cartilage specimens taken from pigs or OA patients. Western blotting, quantitative PCR, and immunohistochemistry were adopted to measure the expression of collagen II (Col II) and matrix metalloproteinases (MMP). DXM significantly restored tumor necrosis factor-alpha (TNF-α)-mediated reduction of collagen II and decreased TNF-α-induced MMP-13 production. To inhibit the synthesis of MMP-13, DXM blocked TNF-α downstream signaling, including I kappa B kinase (IKK)α/β-IκBα-nuclear factor-kappaB (NF-κB) and c-Jun N-terminal kinase (JNK)-activator protein-1 (AP-1) activation. Besides this, DXM protected the CIA mice from severe inflammation and cartilage destruction. DXM seemed to protect cartilage from inflammation-mediated matrix degradation, which is an irreversible status in the disease progression of osteoarthritis. The results suggested that testing DXM as an osteoarthritis therapeutic should be a focus in further research.
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影响因子：
5.8
作者：
Ho, LJ;Lin, LC;Tai, TY
通讯作者：
Tai, TY
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3.7
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