Novel chondrogenic and chondroprotective effects of the natural compound harmine
Novel chondrogenic and chondroprotective effects of the natural compound harmine
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DOI：
10.1016/j.biochi.2012.10.016
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发表时间：
2013-02-01
期刊：
影响因子：
3.9
通讯作者：
Kuboki, Takuo
中科院分区：
文献类型：
--
作者：
Hara, Emilio Satoshi;Ono, Mitsuaki;Kuboki, Takuo
大量的天然化合物已被证明可以调节细胞的行为，与细胞蛋白合作。CCN2/结缔组织生长因子（CTGF）在软骨发育、软骨细胞增殖和分化以及调节细胞外基质代谢中发挥重要作用。先前的研究证实了CCN2对大鼠膝关节关节软骨手术缺损的再生能力。此外，过度表达软骨特异性CCN2的转基因小鼠被证明更能抵抗与衰老相关的软骨退化。我们假设，在软骨细胞中诱导CCN2的小分子可能是增加对衰老相关软骨退化的抵抗力的新候选者，甚至可以纠正OA引起的软骨退行性变化。因此，本研究筛选了一个化合物文库，并鉴定出β -碳碱生物碱毒碱是一种新的CCN2诱导剂，可用于人软骨细胞HCS-2/8细胞和骨关节炎关节软骨细胞。hammine增加软骨标志物aggrecan和COL2 α 1的表达，以及软骨形成的主要调节因子SOX-9的表达。此外，在微块培养中，毒芹碱显著诱导ATDC5软骨前细胞的软骨形成。在TNF α刺激的炎症条件下，研究了hammine的软骨保护作用，hammine被证明可以改善TNF α诱导的CCN2和软骨标志物表达的下降。这些发现揭示了有害生物碱的新软骨形成作用，并表明有害生物碱是一种潜在的预防和/或修复软骨降解的药物。(C) 2012 Elsevier Masson SAS。版权所有。
A significant number of natural compounds have been shown to regulate the behavior of the cells, in collaboration with cellular proteins. CCN2/connective tissue growth factor (CTGF) has been reported to have essential roles in cartilage development, chondrocyte proliferation and differentiation as well as regulation of the extracellular matrix metabolism. Previous studies demonstrated the capability of CCN2 to regenerate surgical defects in articular cartilage of rat knee. Also, transgenic mice over-expressing cartilage-specific CCN2 were shown to be more resistant to aging-related cartilage degradation. We hypothesized that small molecules that induce CCN2 in chondrocytes could be novel candidates to increase the resistance to aging-related cartilage degradation, or even to correct cartilage degenerative changes incurred in OA. Therefore, this study screened a compound library and identified the beta-carboline alkaloid harmine as a novel inducer of CCN2 in human chondrocytic HCS-2/8 cells and osteoarthritic articular chondrocytes. Harmine increased the expression of the cartilage markers aggrecan and COL2 alpha 1, as well as that of the master regulator of chondrogenesis, SOX-9. Moreover, harmine notably induced chondrogenesis of prechondrocytic ATDC5 cells in micromass cultures. The chondroprotective effect of harmine was investigated under inflammatory condition by stimulation with TNF alpha, and harmine was shown to ameliorate TNF alpha-induced decrease in expression of CCN2 and cartilage markers. These findings uncover novel chondrogenic effects of harmine and indicate harmine as a potential drug for prevention and/or repair of cartilage degradation. (C) 2012 Elsevier Masson SAS. All rights reserved.