Alpha 2-Macroglobulin as Dual Regulator for Both Anabolism and Catabolism in the Cartilaginous Endplate of Intervertebral Disc. Issue 6 (15th March 2019)

• Record Type: Journal Article
• Authors: Huang, Bao; Chen, Jian; Zhang, Xuyang; Wang, Jiasheng; Zheng, Zeyu; Shan, Zhi; Liu, Junhui; Zhu, Zhihai; Zhao, Fengdong
• Is Part Of: Spine. Volume 44:Issue 6(2019)
• Publication Date: 2019-03-15
• Subjects: alpha 2-macroglobulin -- anabolism -- cartilaginous endplate -- catabolism -- intervertebral disc; Spine -- Abnormalities -- Periodicals; Spine -- Diseases -- Periodicals; Spine -- Surgery -- Periodicals; 616.73005
• DOI: 10.1097/BRS.0000000000002852
• Languages: English
• ISSNs: 0362-2436

Abstract

Abstract : Study Design: Basic science study. Objective: To illustrate supplemental alpha-2 macroglobulin (α2 M) has beneficial effects on cartilaginous endplates (CEPs) that may slow the progression of intervertebral disc (IVD) degeneration. Summary of Background Data: CEPs play a vital role in progression of intervertebral disc degenerative diseases. However, the ideal and economic therapies for CEPs degeneration are still urgently required. Methods: Firstly, we confirmed degenerative CEP characters by H&E and Safranin O fast green staining and detected increasing level of α2 M and matrix metalloproteinase 13(MMP-13) in degenerative CEP by immunohistochemistry. Then, effects of exogenous α2 M on tumor necrosis factor alpha (TNF-α)-induced CEP catabolic enzyme and anabolic molecules were evaluated by qRT-PCR, Western blotting and ELISA in cultured CEP cells obtained from rats. Furthermore, suppression of α2 M on TNF-α-induced activation of NF-кB signaling pathway was measured by Western blotting and immunofluorescence. In addition, function of α2 M on TNF-α-treated ex vivo IVDs from rats lumbar IVDs was estimated by measuring the expression of MMP-13, Sox9, aggrecan, and type II collagen in CEP area. Results: Compared with normal CEP, level of α2 M was slightly increased in CEP from degenerative patients, whereas MMP-13 was sharply elevated. In vitro, α2 M inhibited expression and activity of MMP-3 or MMP-13 in a dose-dependent manner in rat CEP cells stimulated by TNF-α. The α2 M refrained phosphorylation of IκBα and inhibited nuclear translocation of p65. Finally, supplemental α2 M reduced expression of MMP-13, and promoted expression of Sox9, aggrecan, and type II collagen in CEP area of ex vivo IVDs cultured with TNF-α. Conclusion: α2 M is not sufficiently produced to inactivate higher concentrations of catabolic factor MMP-13 found in the degenerated CEP. Supplemental α2 M protects against the progression of IVD degeneration by inhibiting effects of proinflammatory cytokines. Level of Evidence: N/A Abstract : The features of human CEP degeneration with increased catabolic factors and decreased anabolic factors are verified. CEP cells treated by TNF-α compared with IL-1β show more effective degeneration. Alpha 2-macroglobulin can suppress TNF-α-induced activation of NF-кB signaling pathway in CEP cells, thus alleviating the degeneration of IVD.