A role for TNFα in intervertebral disc degeneration: a non-recoverable catabolic shift.
A role for TNFα in intervertebral disc degeneration: a non-recoverable catabolic shift.
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DOI：
10.1016/j.bbrc.2013.02.034
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发表时间：
2013-03-29
影响因子：
3.1
通讯作者：
Iatridis, James
中科院分区：
文献类型：
--
作者：
Purmessur, D.;Walter, B. A.;Roughley, P. J.;Laudier, D. M.;Hecht, A. C.;Iatridis, James
本研究检查了TNFα对器官培养中整个牛椎间盘的影响及其与椎间盘退变（IDD）特征性变化的相关性，以便为未来治疗提供信息，以减轻疼痛性IDD常见的慢性炎症状态。促炎性细胞因子如TNFα促进椎间盘病理学，并与疼痛性IDD相关的分解代谢表型有关。培养整个牛椎间盘，以检查TNFα处理后的细胞（合成代谢/分解代谢基因表达、细胞活力和衰老，使用β-半乳糖苷酶）和结构（组织学和聚集蛋白聚糖降解）变化。在第7天和第21天评估对照或TNFα培养物;第21天组还包括一个恢复组，TNFα培养7天，随后在基础培养基中培养14天。TNFα在第7天时诱导髓核（NP）和纤维环（AF）的分解代谢和抗合成代谢变化，并持续至第21天，但细胞活力不受影响。数据表明，TNFα增加了聚集蛋白聚糖降解产物，并表明在第21天时β-半乳糖苷酶染色增加，无任何恢复。TNFα处理整个牛椎间盘7天诱导了与人IDD中发生的变性过程相似的变化：聚集蛋白聚糖降解、促炎性细胞因子、促炎性细胞因子和神经生长因子表达增加。TNFα可显著降低体外培养的IVD中的凋亡，其机制可能与细胞衰老有关。因此，结果表明，成功的治疗必须促进炎症和细胞增殖，除了限制炎症。
This study examines the effect of TNFα on whole bovine intervertebral discs in organ culture and its association with changes characteristic of intervertebral disc degeneration (IDD) in order to inform future treatments to mitigate the chronic inflammatory state commonly found with painful IDD. Pro-inflammatory cytokines such as TNFα contribute to disc pathology and are implicated in the catabolic phenotype associated with painful IDD. Whole bovine discs were cultured to examine cellular (anabolic/catabolic gene expression, cell viability and senescence using β-galactosidase) and structural (histology and aggrecan degradation) changes in response to TNFα treatment. Control or TNFα cultures were assessed at 7 and 21 days; the 21 day group also included a Recovery group with 7 days TNFα followed by 14 days in basal media. TNFα induced catabolic and anti-anabolic shifts in the nucleus pulposus (NP) and annulus fibrosus (AF) at 7 days and this persisted until 21 days however cell viability was not affected. Data indicates that TNFα increased aggrecan degradation products and suggests increased β-galactosidase staining at 21 days without any recovery. TNFα treatment of whole bovine discs for 7 days induced changes similar to the degeneration processes that occur in human IDD: aggrecan degradation, increased catabolism, pro-inflammatory cytokines and nerve growth factor expression. TNFα significantly reduced anabolism in cultured IVDs and a possible mechanism may be associated with cell senescence. Results therefore suggest that successful treatments must promote anabolism and cell proliferation in addition to limiting inflammation.
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影响因子：
2.8
作者：
Gabr, Mostafa A.;Jing, Liufang;Helbling, Antonia R.;Sinclair, S. Michael;Allen, Kyle D.;Shamji, Mohammed F.;Richardson, William J.;Fitch, Robert D.;Setton, Lori A.;Chen, Jun
通讯作者：
Chen, Jun
影响因子：
--
作者：
Hiyama, Akihiko;Sakai, Daisuke;Risbud, Makarand V.;Tanaka, Masahiro;Arai, Fumiyuki;Abe, Koichiro;Mochida, Joji
通讯作者：
Mochida, Joji
影响因子：
4.9
作者：
Le Maitre, Christine Lyn;Hoyland, Judith Alison;Freemont, Anthony J
通讯作者：
Freemont, Anthony J
影响因子：
3
作者：
Gruber, Helen E.;Ingram, Jane A.;Hanley, Edward N., Jr.
通讯作者：
Hanley, Edward N., Jr.
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ