I型组蛋白去乙酰化酶抑制剂在阻断软骨退化中的作用

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Abstract Objective: To investigate the protective effect and possible mechanism of I type HDAC inhibitor in cartilage degradation. Methods: An unstable dementabilization of the medial meniscus (DMM) model was used to assess the inhibition of HDAC by trichostatin A (TSA) in vivo. Cytokines, TSA, MS-275, valproic acid and siRNA were applied to human articular chondrocytes (HACs) and sw-1353 hondrosarcocma cells. And RT-PCR was used to confirm how they influence the expression of metalloproteinase. The activity of HDAC inhibitor was tested by western blot. The absorption of cartilage in vitro was examined by a pig’s nasal cartilage explant test. Results: Systemic administration of TSA in the developmental process (DMM) can protect cartilage. TSA, valproic acid, and MS-275 in human articular chondrocytes (HACs) inhibited the expression of MMP1 and MMP13 which was induced by cytokine, and after knocking out each type I HDAC, MMP13 expression which was induced by interleukin-1 decreased. Conclusion: MS-275 inhibition to type I HDAC (HDAC-1, HDAC-2, HDAC-3) and HDACs specificity consumption can inhibit the expression of metalloproteinase induced by cytokines in chondrocytes and PNC explants, thereby inhibiting cartilage absorption. These observations indicate that specific type I HDACs inhibitors can block cartilage degradation to some extent.

Key words： deacetylase inhibitor osteoarthritis cartilage degeneration trichostatin A

Received: 30 July 2018

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	GU Xiaopeng
	CHAO Haichao
	GU Yuequan.

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https://xb.wmu.edu.cn/EN/ OR https://xb.wmu.edu.cn/EN/Y2018/V48/I12/881

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