Carnosic acid attenuates cartilage degeneration through induction of heme oxygenase-1 in human articular chondrocytes.
Carnosic acid attenuates cartilage degeneration through induction of heme oxygenase-1 in human articular chondrocytes.
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DOI：
10.1016/j.ejphar.2018.04.018
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发表时间：
2018-07-05
影响因子：
5
通讯作者：
Adachi N
中科院分区：
文献类型：
--
作者：
Ishitobi H;Sanada Y;Kato Y;Ikuta Y;Shibata S;Yamasaki S;Lotz MK;Matsubara K;Miyaki S;Adachi N
骨关节炎（OA）是一种常见的与年龄相关的疾病，与关节疼痛、活动受限和整体生活质量受损有关。骨性关节炎的治疗目前仅限于疼痛管理和终末期疾病的关节置换术。软骨细胞外基质和细胞的氧化损伤是关节老化和骨性关节炎发病的重要机制。体外和体内OA模型的证据表明，在动物模型中，具有抗氧化特性的药物和天然化合物可降低OA发病机制和OA严重程度的介质的表达。在控制细胞对氧自由基损伤的保护机制的信号通路中，有血红素加氧酶-1 （HO-1）。我们最近报道了HO-1在小鼠模型中降低OA严重程度。这导致了一种假设，即增加HO-1表达的化合物具有治疗OA的潜力。鼠尾草酸（CA）是一种具有氧化活性的天然二萜，通过诱导HO-1来防止软骨变性。CA诱导人关节软骨细胞HO-1和miR-140表达，CA治疗后软骨退行性变减弱。CA诱导的HO-1部分与miR-140结合BTB和CNC同源物1 （BACH1）的3'UTR下调有关。这些发现表明CA通过HO-1上调来减弱软骨退化，并有可能作为OA预防的补充。
Osteoarthritis (OA) is common age-associated disease, and associated with joint pain, mobility limitations and compromised overall quality of life. OA treatment is currently limited to pain management and joint arthroplasty at end stage disease. Oxidative damage to cartilage extracellular matrix and cells is an important mechanism in joint aging and OA pathogenesis. Evidence from in vitro and in vivo models of OA suggests that pharmaceuticals and natural compounds with antioxidant properties reduce expression of mediators of OA pathogenesis and OA severity in animal models. Among the signaling pathways that control cellular protective mechanisms against oxygen radical damage is heme oxygenase-1 (HO-1). We recently report HO-1 reduced OA severity in a mouse model. This led to the hypothesis that compounds that increase HO-1 expression have therapeutic potential in OA. Carnosic acid (CA), a natural diterpene with oxidant activity, is prevents cartilage degeneration though induction of HO-1. CA induced HO-1 and miR-140 expression in human articular chondrocytes, and cartilage degeneration was attenuated by CA treatment. Induced HO-1 by CA was in part associated with downregulation via miR-140 binding to 3’UTR of BTB and CNC homology 1 (BACH1). These findings suggest that CA attenuates cartilage degradation through HO-1 upregulation and has potential as a supplement for OA prevention.
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DOI：
10.3390/molecules15117792
发表时间：
2010-11-03
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Kelsey NA;Wilkins HM;Linseman DA
通讯作者：
Linseman DA
影响因子：
13.5
作者：
Hou, Weihong;Tian, Qing;Zheng, Jianyu;Bonkovsky, Herbert L.
通讯作者：
Bonkovsky, Herbert L.
DOI：
10.1016/j.trsl.2015.06.011
发表时间：
2016-01
期刊：
Translational research : the journal of laboratory and clinical medicine
影响因子：
--
作者：
Ryter SW;Choi AM
通讯作者：
Choi AM
影响因子：
7
作者：
D'Adamo S;Alvarez-Garcia O;Muramatsu Y;Flamigni F;Lotz MK
通讯作者：
Lotz MK
组蛋白脱乙酰酶抑制激活 Nrf2 并预防骨关节炎
影响因子：
4.9
作者：
Cai D;Yin S;Yang J;Jiang Q;Cao W
通讯作者：
Cao W