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Alpha 2-Macroglobulin as Dual Regulator for Both Anabolism and Catabolism in the Cartilaginous Endplate of Intervertebral Disc.
Spine (Phila Pa 1976) 2019; 44(6):E338-E347S

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.

Authors+Show Affiliations

Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.Department of Orthopedic Surgery, Linhai Second People's Hospital, Duqiao, Linhai, Taizhou, China.Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30138255

Citation

Huang, Bao, et al. "Alpha 2-Macroglobulin as Dual Regulator for Both Anabolism and Catabolism in the Cartilaginous Endplate of Intervertebral Disc." Spine, vol. 44, no. 6, 2019, pp. E338-E347.
Huang B, Chen J, Zhang X, et al. Alpha 2-Macroglobulin as Dual Regulator for Both Anabolism and Catabolism in the Cartilaginous Endplate of Intervertebral Disc. Spine. 2019;44(6):E338-E347.
Huang, B., Chen, J., Zhang, X., Wang, J., Zheng, Z., Shan, Z., ... Zhao, F. (2019). Alpha 2-Macroglobulin as Dual Regulator for Both Anabolism and Catabolism in the Cartilaginous Endplate of Intervertebral Disc. Spine, 44(6), pp. E338-E347. doi:10.1097/BRS.0000000000002852.
Huang B, et al. Alpha 2-Macroglobulin as Dual Regulator for Both Anabolism and Catabolism in the Cartilaginous Endplate of Intervertebral Disc. Spine. 2019 03 15;44(6):E338-E347. PubMed PMID: 30138255.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alpha 2-Macroglobulin as Dual Regulator for Both Anabolism and Catabolism in the Cartilaginous Endplate of Intervertebral Disc. AU - Huang,Bao, AU - Chen,Jian, AU - Zhang,Xuyang, AU - Wang,Jiasheng, AU - Zheng,Zeyu, AU - Shan,Zhi, AU - Liu,Junhui, AU - Zhu,Zhihai, AU - Zhao,Fengdong, PY - 2018/8/24/pubmed PY - 2018/8/24/medline PY - 2018/8/24/entrez SP - E338 EP - E347 JF - Spine JO - Spine VL - 44 IS - 6 N2 - 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. SN - 1528-1159 UR - https://www.unboundmedicine.com/medline/citation/30138255/Alpha_2_Macroglobulin_as_Dual_Regulator_for_Both_Anabolism_and_Catabolism_in_the_Cartilaginous_Endplate_of_Intervertebral_Disc_ L2 - http://dx.doi.org/10.1097/BRS.0000000000002852 DB - PRIME DP - Unbound Medicine ER -