RESEARCH PROGRESS OF Wnt/β-catenin AND NUCLEAR FACTOR-KAPPA B PATHWAYS AND THEIR RELEVANCE TO INTERVERTEBRAL DISC DEGENERATION_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

KONG Jingbo ^1,2 , MA Xinlong ^1,2 , WANG Tao ¹ , MA Jianxiong ² , TIAN Peng ¹ , HAN Chao ¹ , ZANG Jiacheng ¹ , LI Pengfei ² , JIANG Hongqiang ²

1The Integration of Traditional and Western Medicinal Academy of Orthopaedics of Tianjin, Tianjin Hospital, Tianjin, 300211, P.R.China;;
2Department of Orthopaedics, Biomechanical Laboratory, General Hospital of Tianjin Medical University. Corresponding author: MA Xinlong, E-mail: orthspinewang@163.com;

Corresponding author：

Keywords：

Wnt/β-catenin Nuclear factor-kappa B; Intervertebral disc degeneration; Signal pathway

DOI：

10.7507/1002-1892.20130333

Video：

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Objective To review the progress of the mechanisms of Wnt/β-catenin and nuclear factor-kappa B (NF-кB) pathways in the process of the intervertebral disc degeneration. Methods The related literature about the mechanisms of Wnt/β-catenin and NF-кB pathways in the process of the intervertebral disc degeneration was reviewed, analyzed, and summarized. Results Wnt/β-catenin and NF-кB pathways are both activated in the process of the intervertebral disc degeneration, and exist interaction. However, the specific mechanisms and interactive mediums of Wnt/β-catenin and NF-кB pathways in the process of the intervertebral disc degeneration are still unclear. Conclusion The mechanisms of Wnt/β-catenin and NF-кB pathways in the process of the intervertebral disc degeneration have to be studied deeply.

Citation： KONG Jingbo,MA Xinlong,WANG Tao,MA Jianxiong,TIAN Peng,HAN Chao,ZANG Jiacheng,LI Pengfei,JIANG Hongqiang. RESEARCH PROGRESS OF Wnt/β-catenin AND NUCLEAR FACTOR-KAPPA B PATHWAYS AND THEIR RELEVANCE TO INTERVERTEBRAL DISC DEGENERATION. Chinese Journal of Reparative and Reconstructive Surgery, 2013, 27(12): 1523-1527. doi: 10.7507/1002-1892.20130333 Copy

1.	Richardson SM, Doyle P, Minogue BM, et al. Increased expression of matrix metalloproteinase-10, nerve growth factor and substance P in the painful degenerate intervertebral disc. Arthritis Res Ther, 2009, 11(4): R126.
2.	Wu Q, Zhu M, Rosier RN, et al. Beta-catenin, cartilage, and osteoarthritis. Ann N Y Acad Sci, 2010, 1192: 344-350.
3.	Behari J. The Wnt/beta-catenin signaling pathway in liver biology and disease. Expert Rev Gastroenterol Hepatol, 2010, 4(6): 745-756.
4.	MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell, 2009, 17(1): 9-26.
5.	Ahn KS, Sethi G, Aggarwal BB. Nuclear factor-kappa B: from clone to clinic. Curr Mol Med, 2007, 7(7): 619-637.
6.	Kondo N, Yuasa T, Shimono K, et al. Intervertebral disc development is regulated by Wnt/β-catenin signaling. Spine (Phila Pa 1976), 2011, 36(8): E513-518.
7.	Nerlich AG, Bachmeier BE, Schleicher E, et al. Immunomorphological analysis of RAGE receptor expression and NF-kappa B activation in tissue samples from normal and degenerated intervertebral discs of various ages. Ann N Y Acad Sci, 2007, 1096: 239-248.
8.	Neumann J, Endermann T, Ehlers S, et al. Inverse relationship of TLR/NF-κB signalling and the Wnt/β-catenin pathway during inflammation: Deciphering the role of Frizzled1 in M.tuberculosis infection. Cell Communication and Signaling, 2009, 7(Suppl 1): A52.
9.	Du Q, Zhang X, Cardinal J, et al. Wnt/beta-catenin signaling regulates cytokine-induced human inducible nitric oxide synthase expression by inhibiting nuclear factor-kappaB activation in cancer cells. Cancer Res, 2009, 69(9): 3764-3771.
10.	Adams MA, Roughley PJ. What is intervertebral disc degeneration, and what causes it? Spine (Phila Pa 1976), 2006, 31(18): 2151-2161.
11.	Ahn SH, Cho YW, Ahn MW, et al. mRNA expression of cytokines and chemokines in herniated lumbar intervertebral discs. Spine (Phila Pa 1976), 2002, 27(9): 911-917.
12.	Le Maitre CL, Freemont AJ, Hoyland JA. The role of interleukin-1 in the pathogenesis of human intervertebral disc degeneration. Arthritis Res Ther, 2005, 7(4): R732-745.
13.	Séguin CA, Pilliar RM, Roughley PJ, et al. Tumor necrosis factor-alpha modulates matrix production and catabolism in nucleus pulposus tissue. Spine (Phila Pa1976), 2005, 30(17): 1940-1948.
14.	Nusse R, Varmre HE. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell, 1982, 31(1): 99-109.
15.	Sharma RP. Wingless a new mutant in Drosophila melanogaster. Drosophila Information Service, 1973, 50: 134.
16.	Seto ES, Bellen HJ. The ins and outs of wingless signaling. Trends Cell Biol, 2004, 14(1): 45-53.
17.	Sen R, Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell, 1986, 46(5): 705-716.
18.	Mankan AK, Lawless MW, Gray SG, et al. NF-kappaB regulation: the nuclear response. J Cell Mol Med, 2009, 13(4): 631-643.
19.	王晶. 经典 Wnt/β-catenin 信号通路在椎间盘退变中的作用及机制研究. 武汉: 华中科技大学, 2009.
20.	Hiyama A, Sakai D, Risbud M, et al. Enhancement of intervertebral disc cell senescence by WNT/β-catenin signaling induced matrix metalloproteinase expression. Arthritis Rheum, 2010, 62(10): 3036-3047.
21.	Smolders LA, Meij BP, Onis D, et al. Gene expression profiling of early intervertebral disc degeneration reveals a down-regulation of canonical Wnt signaling and caveolin-1 expression: implications for development of regenerative strategies. Arthritis Res Ther, 2013, 15 (1): R23.
22.	Mengshol JA, Vincenti MP, Coon CI, et al. Interleukin-1 induction of collagenase 3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38, c-Jun N-terminal kinase, and nuclear factor kappaB: differential regulation of collagenase 1 and collagenase 3. Arthritis Rheum, 2000, 43(19): 801-811.
23.	吴庆能, 雷刚刚, 钟青山, 等. 退变椎间盘中NF-κB、MMP-13的表达及意义. 实用临床医学, 2009, 10(2): 5-7.
24.	Yu ZG, Xu N, Wang WB, et al. Interleukin-1 inhibits Sox9 and collagen type II expression via nuclear factor-κB in the cultured human intervertebral disc cells. Chin Med J (Engl), 2009, 122(20): 2483-2488.
25.	原野, 赵静, 李永民. 核因子κB和肿瘤坏死因子仅在正常椎间盘及其退行性变组织中的表达. 中国临床康复, 2006, 10(28): 22, 25.
26.	Wang P, Qiu W, Dudgeon C, et al. PUMA is directly activated by NF-κB and contributes to TNF-alpha-induced apoptosis. Cell Death Differ, 2009, 16(9): 1192-1202.
27.	Wang J, Markova D, Anderson DG, et al. TNF-α and IL-1β promote a disintegrin-like and metalloprotease with thrombospondin type I motif-5-mediated aggrecan degradation through syndecan-4 in intervertebral disc. J Biol Chem, 2011, 286(46): 39738-39749.
28.	Nasto LA, Seo HY, Robinson AR, et al. Issls prize winner: Inhibition of NF-κB activity ameliorates age-associated disc degeneration in a mouse model of accelerated aging. Spine (Phila Pa 1976), 2012, 37(21): 1819-1825.
29.	Fujita N, Markova D, Anderson DG, et al. Expression of prolyl hydroxylases (PHDs) is selectively controlled by HIF-1 and HIF-2 proteins in nucleus pulposus cells of the intervertebral disc: distinct roles of PHD2 and PHD3 proteins in controlling HIF-1α activity in hypoxia. Biol Chem, 2012, 287(20): 16975-16986.
30.	Fujita N, Chiba K, Shapiro IM, et al. HIF-1α and HIF-2α degradation is differentially regulated in nucleus pulposus cells of the intervertebral disc. J Bone Miner Res, 2012, 27(2): 401-412.
31.	Fujita N, Gogate SS, Chiba K, et al. Prolylhydroxylase-3 (PHD3) modulates catabolic effects of tumor necrosis factor-α (TNF-α) on cells of the nucleus pulposus through co-activation of nuclear factor κB (NF-κB)/p65 signaling. J Biol Chem, 2012, 287(47): 39942-39953.
32.	Moreau M, Mourah S, Dosquet C. β-Catenin and NF-κB cooperate to regulate the uPA/uPAR system in cancer cells. Int J Cancer, 2011, 128(6): 1280-1292.
33.	Carayol N, Wang CY. IKKalpha stabilizes cytosolic beta-catenin by inhibiting both canonical and non-canonical degradation pathways. Cell Signal, 2006, 18(11): 1941-1946.
34.	Lamberti C, Lin KM, Yamamoto Y, et al. Regulation of beta-catenin function by the IkappaB kinases. J Biol Cell, 2001, 276(45): 42276-42286.
35.	Albanese C, Wu K, D’Amico M, et al. IKKalpha regulates mitogenic signaling through transcriptional induction of cyclin D1 via Tcf. Mol Biol Cell, 2003, 14(2): 585-599.
36.	Deng J, Miller SA, Wang HY, et al. beta-catenin interacts with and inhibits NF-kappa B in human colon and breast cancer. Cancer Cell, 2002, 2(4): 323-334.
37.	Deng J, Xia W, Miller SA, et al. Crossregulation of NF-κB by the APC/GSK-3beta/beta-catenin pathway. Mol Carcinog, 2004, 39(3): 139-146.
38.	Nejak-Bowen K, Kikuchi A, Monga SP. Beta-catenin-NF-κB interactions in murine hepatocytes: a complex to die for it . Hepatology, 2013, 57(2): 763-774.
39.	Deregowski V, Delhalle S, Benoit V, et al. Identification of cytokine-induced nuclear factor-kappaB target genes in ovarian and breast cancer cells. Biochem Pharmacol, 2002, 64(5-6): 873-881.
40.	Galbiati F, Volonate D, Brown AM, et al. Caveolin-1 expression inhibits Wnt/beta-catenin/Lef-1 signaling by recruiting beta-catenin to caveolae membrane domains. J Biol Chem, 2000, 275(30): 23368-23377.
41.	Wang CY, Mayo MW, Korneluk RG, et al. NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science, 1998, 281(5383): 1680-1683.
42.	Greenspan EJ, Madigan JP, Boardman LA, et al. Ibuprofen inhibits activation of nuclear β-catenin in human colon adenomas and induces the phosphorylation of GSK-3β. Cancer Prev Res (Phila), 2011, 4(1): 161-171.
43.	Garrean S, Gao XP, Brovkovych V, et al. Caveolin-1 regulates NF-kappaB activation and lung inflammatory response to sepsis induced by lipopolysaccharide. J Immunol, 2006, 177(7): 4853-4860.
44.	Ichimura A, Ruike Y, Terasawa K, et al. miRNAs and regulation of cell signaling. FEBS J, 2011, 278(10): 1610-1618.
45.	Wang HQ, Yu XD, Liu ZH, et al. Deregulated miR-155 promotes Fas-mediated apoptosis in human intervertebral disc degeneration by targeting FADD and caspase-3. J Pathol, 2011, 225(2): 232-242.
46.	Roccaro AM, Sacco A, Chen C, et al. microRNA expression in the biology, prognosis, and therapy of Waldenström macroglobulinemia. Blood, 2009, 113(18): 4391-4402.
47.	Zhang Y, Wei W, Cheng N, et al. Hepatitis C virus-induced up-regulation of microRNA-155 promotes hepatocarcinogenesis by activating Wnt signaling. Hepatology, 2012, 56(5): 1631-1640.
48.	Lu F, Weidmer A, Liu CG, et al. Epstein-Barr virus-induced miR-155 attenuates NF-κB signaling and stabilizes latent virus persistence. J Virol, 2008, 82(21): 10436-10443.
49.	Gortazar AR, Martin-Millan M, Bravo B, et al. Crosstalk between Caveolin-1/Extracellular Signal-regulated Kinase (ERK) and β-Catenin Survival Pathways in Osteocyte Mechanotransduction. J Biol Chem, 2013, 288(12): 8168-8175.

1. Richardson SM, Doyle P, Minogue BM, et al. Increased expression of matrix metalloproteinase-10, nerve growth factor and substance P in the painful degenerate intervertebral disc. Arthritis Res Ther, 2009, 11(4): R126.
2. Wu Q, Zhu M, Rosier RN, et al. Beta-catenin, cartilage, and osteoarthritis. Ann N Y Acad Sci, 2010, 1192: 344-350.
3. Behari J. The Wnt/beta-catenin signaling pathway in liver biology and disease. Expert Rev Gastroenterol Hepatol, 2010, 4(6): 745-756.
4. MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell, 2009, 17(1): 9-26.
5. Ahn KS, Sethi G, Aggarwal BB. Nuclear factor-kappa B: from clone to clinic. Curr Mol Med, 2007, 7(7): 619-637.
6. Kondo N, Yuasa T, Shimono K, et al. Intervertebral disc development is regulated by Wnt/β-catenin signaling. Spine (Phila Pa 1976), 2011, 36(8): E513-518.
7. Nerlich AG, Bachmeier BE, Schleicher E, et al. Immunomorphological analysis of RAGE receptor expression and NF-kappa B activation in tissue samples from normal and degenerated intervertebral discs of various ages. Ann N Y Acad Sci, 2007, 1096: 239-248.
8. Neumann J, Endermann T, Ehlers S, et al. Inverse relationship of TLR/NF-κB signalling and the Wnt/β-catenin pathway during inflammation: Deciphering the role of Frizzled1 in M.tuberculosis infection. Cell Communication and Signaling, 2009, 7(Suppl 1): A52.
9. Du Q, Zhang X, Cardinal J, et al. Wnt/beta-catenin signaling regulates cytokine-induced human inducible nitric oxide synthase expression by inhibiting nuclear factor-kappaB activation in cancer cells. Cancer Res, 2009, 69(9): 3764-3771.
10. Adams MA, Roughley PJ. What is intervertebral disc degeneration, and what causes it? Spine (Phila Pa 1976), 2006, 31(18): 2151-2161.
11. Ahn SH, Cho YW, Ahn MW, et al. mRNA expression of cytokines and chemokines in herniated lumbar intervertebral discs. Spine (Phila Pa 1976), 2002, 27(9): 911-917.
12. Le Maitre CL, Freemont AJ, Hoyland JA. The role of interleukin-1 in the pathogenesis of human intervertebral disc degeneration. Arthritis Res Ther, 2005, 7(4): R732-745.
13. Séguin CA, Pilliar RM, Roughley PJ, et al. Tumor necrosis factor-alpha modulates matrix production and catabolism in nucleus pulposus tissue. Spine (Phila Pa1976), 2005, 30(17): 1940-1948.
14. Nusse R, Varmre HE. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell, 1982, 31(1): 99-109.
15. Sharma RP. Wingless a new mutant in Drosophila melanogaster. Drosophila Information Service, 1973, 50: 134.
16. Seto ES, Bellen HJ. The ins and outs of wingless signaling. Trends Cell Biol, 2004, 14(1): 45-53.
17. Sen R, Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell, 1986, 46(5): 705-716.
18. Mankan AK, Lawless MW, Gray SG, et al. NF-kappaB regulation: the nuclear response. J Cell Mol Med, 2009, 13(4): 631-643.
19. 王晶. 经典 Wnt/β-catenin 信号通路在椎间盘退变中的作用及机制研究. 武汉: 华中科技大学, 2009.
20. Hiyama A, Sakai D, Risbud M, et al. Enhancement of intervertebral disc cell senescence by WNT/β-catenin signaling induced matrix metalloproteinase expression. Arthritis Rheum, 2010, 62(10): 3036-3047.
21. Smolders LA, Meij BP, Onis D, et al. Gene expression profiling of early intervertebral disc degeneration reveals a down-regulation of canonical Wnt signaling and caveolin-1 expression: implications for development of regenerative strategies. Arthritis Res Ther, 2013, 15 (1): R23.
22. Mengshol JA, Vincenti MP, Coon CI, et al. Interleukin-1 induction of collagenase 3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38, c-Jun N-terminal kinase, and nuclear factor kappaB: differential regulation of collagenase 1 and collagenase 3. Arthritis Rheum, 2000, 43(19): 801-811.
23. 吴庆能, 雷刚刚, 钟青山, 等. 退变椎间盘中NF-κB、MMP-13的表达及意义. 实用临床医学, 2009, 10(2): 5-7.
24. Yu ZG, Xu N, Wang WB, et al. Interleukin-1 inhibits Sox9 and collagen type II expression via nuclear factor-κB in the cultured human intervertebral disc cells. Chin Med J (Engl), 2009, 122(20): 2483-2488.
25. 原野, 赵静, 李永民. 核因子κB和肿瘤坏死因子仅在正常椎间盘及其退行性变组织中的表达. 中国临床康复, 2006, 10(28): 22, 25.
26. Wang P, Qiu W, Dudgeon C, et al. PUMA is directly activated by NF-κB and contributes to TNF-alpha-induced apoptosis. Cell Death Differ, 2009, 16(9): 1192-1202.
27. Wang J, Markova D, Anderson DG, et al. TNF-α and IL-1β promote a disintegrin-like and metalloprotease with thrombospondin type I motif-5-mediated aggrecan degradation through syndecan-4 in intervertebral disc. J Biol Chem, 2011, 286(46): 39738-39749.
28. Nasto LA, Seo HY, Robinson AR, et al. Issls prize winner: Inhibition of NF-κB activity ameliorates age-associated disc degeneration in a mouse model of accelerated aging. Spine (Phila Pa 1976), 2012, 37(21): 1819-1825.
29. Fujita N, Markova D, Anderson DG, et al. Expression of prolyl hydroxylases (PHDs) is selectively controlled by HIF-1 and HIF-2 proteins in nucleus pulposus cells of the intervertebral disc: distinct roles of PHD2 and PHD3 proteins in controlling HIF-1α activity in hypoxia. Biol Chem, 2012, 287(20): 16975-16986.
30. Fujita N, Chiba K, Shapiro IM, et al. HIF-1α and HIF-2α degradation is differentially regulated in nucleus pulposus cells of the intervertebral disc. J Bone Miner Res, 2012, 27(2): 401-412.
31. Fujita N, Gogate SS, Chiba K, et al. Prolylhydroxylase-3 (PHD3) modulates catabolic effects of tumor necrosis factor-α (TNF-α) on cells of the nucleus pulposus through co-activation of nuclear factor κB (NF-κB)/p65 signaling. J Biol Chem, 2012, 287(47): 39942-39953.
32. Moreau M, Mourah S, Dosquet C. β-Catenin and NF-κB cooperate to regulate the uPA/uPAR system in cancer cells. Int J Cancer, 2011, 128(6): 1280-1292.
33. Carayol N, Wang CY. IKKalpha stabilizes cytosolic beta-catenin by inhibiting both canonical and non-canonical degradation pathways. Cell Signal, 2006, 18(11): 1941-1946.
34. Lamberti C, Lin KM, Yamamoto Y, et al. Regulation of beta-catenin function by the IkappaB kinases. J Biol Cell, 2001, 276(45): 42276-42286.
35. Albanese C, Wu K, D’Amico M, et al. IKKalpha regulates mitogenic signaling through transcriptional induction of cyclin D1 via Tcf. Mol Biol Cell, 2003, 14(2): 585-599.
36. Deng J, Miller SA, Wang HY, et al. beta-catenin interacts with and inhibits NF-kappa B in human colon and breast cancer. Cancer Cell, 2002, 2(4): 323-334.
37. Deng J, Xia W, Miller SA, et al. Crossregulation of NF-κB by the APC/GSK-3beta/beta-catenin pathway. Mol Carcinog, 2004, 39(3): 139-146.
38. Nejak-Bowen K, Kikuchi A, Monga SP. Beta-catenin-NF-κB interactions in murine hepatocytes: a complex to die for it . Hepatology, 2013, 57(2): 763-774.
39. Deregowski V, Delhalle S, Benoit V, et al. Identification of cytokine-induced nuclear factor-kappaB target genes in ovarian and breast cancer cells. Biochem Pharmacol, 2002, 64(5-6): 873-881.
40. Galbiati F, Volonate D, Brown AM, et al. Caveolin-1 expression inhibits Wnt/beta-catenin/Lef-1 signaling by recruiting beta-catenin to caveolae membrane domains. J Biol Chem, 2000, 275(30): 23368-23377.
41. Wang CY, Mayo MW, Korneluk RG, et al. NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science, 1998, 281(5383): 1680-1683.
42. Greenspan EJ, Madigan JP, Boardman LA, et al. Ibuprofen inhibits activation of nuclear β-catenin in human colon adenomas and induces the phosphorylation of GSK-3β. Cancer Prev Res (Phila), 2011, 4(1): 161-171.
43. Garrean S, Gao XP, Brovkovych V, et al. Caveolin-1 regulates NF-kappaB activation and lung inflammatory response to sepsis induced by lipopolysaccharide. J Immunol, 2006, 177(7): 4853-4860.
44. Ichimura A, Ruike Y, Terasawa K, et al. miRNAs and regulation of cell signaling. FEBS J, 2011, 278(10): 1610-1618.
45. Wang HQ, Yu XD, Liu ZH, et al. Deregulated miR-155 promotes Fas-mediated apoptosis in human intervertebral disc degeneration by targeting FADD and caspase-3. J Pathol, 2011, 225(2): 232-242.
46. Roccaro AM, Sacco A, Chen C, et al. microRNA expression in the biology, prognosis, and therapy of Waldenström macroglobulinemia. Blood, 2009, 113(18): 4391-4402.
47. Zhang Y, Wei W, Cheng N, et al. Hepatitis C virus-induced up-regulation of microRNA-155 promotes hepatocarcinogenesis by activating Wnt signaling. Hepatology, 2012, 56(5): 1631-1640.
48. Lu F, Weidmer A, Liu CG, et al. Epstein-Barr virus-induced miR-155 attenuates NF-κB signaling and stabilizes latent virus persistence. J Virol, 2008, 82(21): 10436-10443.
49. Gortazar AR, Martin-Millan M, Bravo B, et al. Crosstalk between Caveolin-1/Extracellular Signal-regulated Kinase (ERK) and β-Catenin Survival Pathways in Osteocyte Mechanotransduction. J Biol Chem, 2013, 288(12): 8168-8175.

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RESEARCH PROGRESS OF Wnt/β-catenin AND NUCLEAR FACTOR-KAPPA B PATHWAYS AND THEIR RELEVANCE TO INTERVERTEBRAL DISC DEGENERATION

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