Collagen type II is downregulated in the degenerative nucleus pulposus and contributes to the degeneration and apoptosis of human nucleus pulposus cells.

Collagen type II is downregulated in the degenerative nucleus pulposus and contributes to the degeneration and apoptosis of human nucleus pulposus cells.
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II型胶原蛋白在退变髓核中下调并导致人髓核细胞变性和凋亡

DOI:
10.3892/mmr.2017.7178
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发表时间:
2017-10
影响因子:
3.4
通讯作者:
Huang D
Huang D
中科院分区:
医学4区
文献类型:
--
作者:
Lian C;Gao B;Wu Z;Qiu X;Peng Y;Liang A;Xu C;Su P;Huang D

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退行性椎间盘疾病(DDD)是一种常见的退行性疾病,主要发生在髓核(NP)内。迄今为止,DDD的发病机制仍不清楚,并且由于没有有效的治疗策略可用于靶向其病理过程,DDD仍用远远不够的对症干预治疗。II型胶原蛋白是NP的主要基质组分之一,并且被认为是NP稳态所必需的。然而,II型胶原蛋白影响NP细胞的具体机制仍然未知。在本研究中,II型胶原蛋白的表达检测使用免疫组化分析和定量聚合酶链反应,并证明是显着下调与非退行性对照组相比,从DDD患者的NP组织。为了进一步探索体外机制,使用白细胞介素(IL)-1β刺激诱导人NP细胞系的变性。IL-1β刺激上调了分解代谢标志物基质金属蛋白酶13(MMP 13)和具有血小板反应蛋白基序4的去整合素和金属蛋白酶(ADAMTS 4)的mRNA和蛋白水平,同时下调了合成代谢标志物聚集蛋白聚糖和II型胶原蛋白。然而,添加纯化的II型胶原蛋白防止了这种IL-1β诱导的NP细胞代谢紊乱。此外,IL-1β刺激显著促进NP细胞的凋亡,而II型胶原处理降低凋亡率和切割的caspase-3蛋白水平。总之,II型胶原蛋白通过其抗分解代谢、促合成代谢和抗凋亡作用,在抑制NP细胞变性方面表现出保护作用,这表明它可能是一种有前途的用于预防和治疗DDD的治疗剂。
Degenerative disc disease (DDD) is a common degenerative condition initiated mainly within the nucleus pulposus (NP). To date, the etiopathogenesis of DDD remains unclear, and because no effective therapeutic strategies are available to target its pathological processes, DDD is still treated with symptomatic interventions that are far from adequate. Collagen type II is one of the major matrix components of the NP, and is considered to be essential to NP homeostasis. However, the specific mechanisms by which collagen type II influences NP cells remain unknown. In the present study, collagen type II expression was detected using immunohistochemistry analysis and quantitative polymerase chain reaction, and it was demonstrated to be significantly downregulated in NP tissues from patients with DDD compared with nondegenerative controls. To further explore the mechanism in vitro, interleukin (IL)-1β stimulation was used to induce degeneration of a human NP cell line. IL-1β stimulation upregulated both the mRNA and protein levels of the catabolic markers matrix metalloproteinase 13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4), while it downregulated the anabolic makers aggrecan and collagen type II. However, addition of purified collagen type II prevented this IL-1β-induced metabolic disturbance of the NP cells. Furthermore, IL-1β stimulation significantly promoted apoptosis in NP cells, while collagen type II treatment decreased the apoptotic rate and the protein levels of cleaved caspase-3. In conclusion, collagen type II exhibited protective effects in suppressing NP cell degeneration through its anticatabolic, proanabolic and antiapoptotic effects, suggesting that it may be a promising therapeutic agent for the prevention and treatment of DDD.
DOI: 10.3390/ijms160920344
发表时间: 2015-08-27
影响因子: 5.6
作者:
Zhou X;Tao Y;Liang C;Zhang Y;Li H;Chen Q
通讯作者: Chen Q
DOI: 10.1016/s0140-6736(12)61729-2
发表时间: 2012-12-15
期刊: Lancet (London, England)
影响因子: --
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DOI: 10.1016/j.spinee.2012.02.027
发表时间: 2013-03
期刊: The spine journal : official journal of the North American Spine Society
影响因子: --
作者:
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影响因子: --
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