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European Spine Journal

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01-11-2013 | Original Article

Relationship between neovascularization and degenerative changes in herniated lumbar intervertebral discs

Authors: Tõnu Rätsep, Ave Minajeva, Toomas Asser

Published in: European Spine Journal | Issue 11/2013

Abstract

Purpose

Lumbar disc degeneration may be associated with intensity of neovascularization in disc herniations. Our study was designed to evaluate how much the severity of histodegeneration is related to the development of neovascularization and to the level of pleiotrophin in the herniated lumbar discs.

Methods

Surgically excised lumbar disc specimens were obtained from 29 patients with noncontained (i.e., extruding through the posterior longitudinal ligament) and 21 patients with contained disc herniations. The histodegeneration scores and levels of neovascularization were estimated according to semiquantitative analysis in lumbar disc and endplate samples. Immunohistochemical staining were performed to identify the newly formed blood vessels and to detect the presence of pleiotrophin in the specimens.

Results

Higher levels of disc and endplate neovascularity were registered in noncontained herniations. The level of neovascularization was significantly related to the score of histodegeneration in the herniated disc tissues but not in the endplate specimens. Both contained and noncontained herniations had the highest values of histodegeneration in conjunction with the highest level of neovascularization but the relations between neovascularity and degenerative changes remained to be significant only in the group of noncontained herniations. Registration or frequency of pleiotrophin positive cells did not correlate significantly with histodegeneration or level of neovascularization in the disc samples.

Conclusion

Severe histodegeneration of the lumbar disc herniations is associated with enhanced neovascularization and potentially also spontaneous regression of the herniated tissue.

Kobayashi S, Meir A, Kokubo Y, Uchida K, Takeno K, Miyazaki T, Yayama T, Kubota M, Nomura E, Mwaka E, Baba H (2009) Ultrastructural analysis on lumbar disc herniation using surgical specimens: role of neovascularization and macrophages in hernias. Spine 34(7):655–662PubMedCrossRef

Koike Y, Uzuki M, Kokubun S, Sawai T (2003) Angiogenesis and inflammatory cell infiltration in lumbar disc herniation. Spine 28(17):1928–1933PubMedCrossRef

Pai RR, D’sa B, Raghuveer CV, Kamath A (1999) Neovascularization of nucleus pulposus. A diagnostic feature of intervertebral disc prolapse. Spine 24(8):739–741PubMedCrossRef

Carreon LY, Ito T, Yamada M, Uchiyama S, Takahashi HE (1997) Neovascularization induced by anulus and its inhibition by cartilage endplate. Its role in disc absorption. Spine 22(13):1429–1434PubMedCrossRef

Karamouzian S, Eskandary H, Faramarzee M, Saba M, Safizade H, Ghadipasha M, Malekpoor AR, Ohadi A (2010) Frequency of lumbar intervertebral disc calcification and angiogenesis, and their correlation with clinical, surgical, and magnetic resonance imaging findings. Spine 35(8):881–886PubMedCrossRef

Kato T, Haro H, Komori H, Shinomiya K (2004) Sequential dynamics of inflammatory cytokine, angiogenesis inducing factor and matrix degrading enzymes during spontaneous resorption of the herniated disc. J Orthop Res 22(4):895–900PubMedCrossRef

Matsui Y, Maeda M, Nakagami W, Iwata H (1998) The involvement of matrix metalloproteinases and inflammation in lumbar disc herniation. Spine 23(8):863–869PubMedCrossRef

Peng B, Hao J, Hou S, Wu W, Jiang D, Fu X, Yang Y (2006) Possible pathogenesis of painful intervertebral disc degeneration. Spine 31(5):560–566PubMedCrossRef

Repanti M, Korovessis PG, Stamatakis MV, Spastris P, Kosti P (1998) Evolution of disc degeneration in lumbar spine: a comparative histological study between herniated and postmortem retrieved disc specimens. J Spinal Disord 11(1):41–45PubMedCrossRef

10.

Vernon-Roberts B, Moore RJ, Fraser RD (2007) The natural history of age-related disc degeneration: the pathology and sequelae of tears. Spine 32(25):2797–2804PubMedCrossRef

11.

Boos N, Weissbach S, Rohrbach H, Weiler C, Spratt KF, Nerlich AG (2002) Classification of age-related changes in lumbar intervertebral discs: 2002 Volvo award in basic science. Spine 27(23):2631–2644PubMedCrossRef

12.

Nerlich AG, Schaaf R, Wälchli B, Boos N (2007) Temporo-spatial distribution of blood vessels in human lumbar intervertebral discs. Eur Spine J 16(4):547–555PubMedCrossRef

13.

Ikeda T, Nakamura T, Kikuchi T, Umeda S, Senda H, Takagi K (1996) Pathomechanism of spontaneous regression of the herniated lumbar disc: histologic and immunohistochemical study. J Spinal Disord 9(2):136–140PubMedCrossRef

14.

Johnson WE, Caterson B, Eisenstein SM, Roberts S (2005) Human intervertebral disc aggrecan inhibits endothelial cell adhesion and cell migration in vitro. Spine 30(10):1139–1147PubMedCrossRef

15.

Johnson WE, Eisenstein SM, Roberts S (2001) Cell cluster formation in degenerate lumbar intervertebral discs is associated with increased disc cell proliferation. Connect Tissue Res 42(3):197–207PubMedCrossRef

16.

Haro H, Kato T, Komori H, Osada M, Shinomiya K (2002) Vascular endothelial growth factor (VEGF)-induced angiogenesis in herniated disc resorption. J Orthop Res 20(3):409–415PubMedCrossRef

17.

Minamide A, Hashizume H, Yoshida M, Kawakami M, Hayashi N, Tamaki T (1999) Effects of basic fibroblast growth factor on spontaneous resorption of herniated intervertebral discs. An experimental study in the rabbit. Spine 24(10):940–945PubMedCrossRef

18.

Johnson WE, Patterson AM, Eisenstein SM, Roberts S (2007) The presence of pleiotrophin in the human intervertebral disc is associated with increased vascularization: an immunohistologic study. Spine 32(12):1295–1302PubMedCrossRef

19.

Neidlinger-Wilke C, Liedert A, Wuertz K, Buser Z, Rinkler C, Käfer W, Ignatius A, Claes L, Roberts S, Johnson WE (2009) Mechanical stimulation alters pleiotrophin and aggrecan expression by human intervertebral disc cells and influences their capacity to stimulate endothelial migration. Spine 34(7):663–669PubMedCrossRef

20.

Rutges J, Creemers LB, Dhert W, Milz S, Sakai D, Mochida J, Alini M, Grad S (2010) Variations in gene and protein expression in human nucleus pulposus in comparison with annulus fibrosus and cartilage cells: potential associations with aging and degeneration. Osteoarthr Cartil 18(3):416–423PubMedCrossRef

21.

Papadimitriou E, Mikelis C, Lampropoulou E, Koutsioumpa M, Theochari K, Tsirmoula S, Theodoropoulou C, Lamprou M, Sfaelou E, Vourtsis D, Boudouris P (2009) Roles of pleiotrophin in tumor growth and angiogenesis. Eur Cytokine Netw 20(4):180–190PubMed

22.

Ozaki S, Muro T, Ito S, Mizushima M (1999) Neovascularization of the outermost area of herniated lumbar intervertebral discs. J Orthop Sci 4(4):286–292PubMedCrossRef

23.

Haro H, Shinomiya K, Komori H, Okawa A, Saito I, Miyasaka N, Furuya K (1996) Upregulated expression of chemokines in herniated nucleus pulposus resorption. Spine 21(14):1647–1652PubMedCrossRef

24.

Kikuchi T, Nakamura T, Ikeda T, Ogata H, Takagi K (1998) Monocyte chemoattractant protein-1 in the intervertebral disc. A histologic experimental model. Spine 23(10):1091–1099PubMedCrossRef

25.

Rothoerl RD, Woertgen C, Holzschuh M, Rueschoff J, Brawanski A (1998) Is there a clinical correlate to the histologic evidence of inflammation in herniated lumbar disc tissue? Spine 23(11):1197–1200PubMedCrossRef

26.

Osti OL, Vernon-Roberts B, Moore R, Fraser RD (1992) Annular tears and disc degeneration in the lumbar spine. A post-mortem study of 135 discs. J Bone Jt Surg Br 74(5):678–682

27.

Koch AE, Nickoloff BJ, Holgersson J, Seed B, Haines GK, Burrows JC, Leibovich SJ (1994) 4A11, a monoclonal antibody recognizing a novel antigen expressed on aberrant vascular endothelium. Upregulation in an in vivo model of contact dermatitis. Am J Pathol 144(2):244–259PubMed

28.

Thornalley PJ (1998) Cell activation by glycated proteins. AGE receptors, receptor recognition factors and functional classification of AGEs. Cell Mol Biol (Noisy-le-grand) 44:1013–1023

29.

Tolonen J, Grönblad M, Virri J, Seitsalo S, Rytömaa T, Karaharju E (2001) Transforming growth factor beta receptor induction in herniated intervertebral disc tissue: an immunohistochemical study. Eur Spine J 10(2):172–176PubMedCrossRef

30.

Kokubo Y, Uchida K, Kobayashi S, Yayama T, Sato R, Nakajima H, Takamura T, Mwaka E, Orwotho N, Bangirana A, Baba H (2008) Herniated and spondylotic intervertebral discs of the human cervical spine: histological and immunohistological findings in 500 en bloc surgical samples. Laboratory investigation. J Neurosurg Spine 9(3):285–295PubMedCrossRef

31.

Zigouris A, Batistatou A, Alexiou GA, Pachatouridis D, Mihos E, Drosos D, Fotakopoulos G, Doukas M, Voulgaris S, Kyritsis AP (2011) Correlation of matrix metalloproteinases-1 and -3 with patient age and grade of lumbar disc herniation. J Neurosurg Spine 14(2):268–272PubMedCrossRef

32.

Gruber HE, Ashraf N, Kilburn J, Williams C, Norton HJ, Gordon BE, Hanley EN Jr (2005) Vertebral endplate architecture and vascularization: application of micro-computerized tomography, a vascular tracer, and immunocytochemistry in analyses of disc degeneration in the aging sand rat. Spine 30(23):2593–2600PubMedCrossRef

Title: Relationship between neovascularization and degenerative changes in herniated lumbar intervertebral discs
Authors: Tõnu Rätsep
Ave Minajeva
Toomas Asser
Publication date: 01-11-2013
Publisher: Springer Berlin Heidelberg
Published in: European Spine Journal / Issue 11/2013
Print ISSN: 0940-6719
Electronic ISSN: 1432-0932
DOI: https://doi.org/10.1007/s00586-013-2842-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Relationship between neovascularization and degenerative changes in herniated lumbar intervertebral discs

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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