Heme oxygenase-1 attenuates IL-1β induced alteration of anabolic and catabolic activities in intervertebral disc degeneration

被引：34

作者：

Hu, Bo ^{[1
]}

Shi, Changgui ^{[1
]}

Xu, Chen ^{[1
]}

Cao, Peng ^{[1
]}

Tian, Ye ^{[1
]}

Zhang, Ying ^{[1
]}

Deng, Lianfu ^{[2
]}

Chen, Huajiang ^{[1
]}

Yuan, Wen ^{[1
]}

机构：

[1] Second Mil Med Univ, Changzheng Hosp, Dept Spinal Surg, 415 Feng Yang Rd, Shanghai 200003, Peoples R China

[2] Shanghai Jiao Tong Univ, Sch Med, Shanghai Ruijin Hosp, Shanghai Inst Orthopaed & Traumatol,Shanghai Key, Shanghai 200030, Peoples R China

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

关键词：

NUCLEUS PULPOSUS CELLS; NF-KAPPA-B; TNF-ALPHA; MATRIX METALLOPROTEINASES; UP-REGULATION; INFLAMMATORY CYTOKINES; EXTRACELLULAR-MATRIX; EXPRESSION; MAPK; DEGRADATION;

D O I：

10.1038/srep21190

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Intervertebral disc degeneration (IDD) is characterized by disordered extracellular matrix (ECM) metabolism, implicating subdued anabolism and enhanced catabolic activities in the nucleus pulposus (NP) of discs. Pro-inflammatory cytokines such as interleukin-1 beta (IL-1 beta) are considered to be potent mediators of ECM breakdown. Hemeoxygenase-1 (HO-1) has been reported to participate in cellular anti-inflammatory processes. The purpose of this study was to investigate HO-1 modulation of ECM metabolism in human NP cells under IL-1 beta stimulation. Our results revealed that expression of HO-1 decreased considerably during IDD progression. Induction of HO-1 by cobalt protoporphyrin IX attenuated the inhibition of sulfate glycosaminoglycan and collagen type II (COL-II) synthesis and ameliorated the reduced expressions of aggrecan, COL-II, SOX-6 and SOX-9 mediated by IL-1 beta. Induction of HO-1 also reversed the effect of IL-1 beta on expression of the catabolic markers matrix metalloproteinases-1, 3, 9 and 13. This was combined with inhibition of the activation of mitogenactivated protein kinase signaling. These findings suggest that HO-1 might play a pivotal role in IDD, and that manipulating HO-1 expression might mitigate the impairment of ECM metabolism in NP, thus potentially offering a novel therapeutic approach to the treatment of IDD.

引用

页数：14

共 57 条

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