Trauma induces apoptosis in human thoracolumbar intervertebral discs
Tóm tắt
Vertebral fractures resulting from high energy trauma often comprise the risk of posttraumatic degenerative changes in the affected intervertebral discs (IVD). Particularly in conservatively treated patients, or in cases after implant removal of an exclusively posterior stabilization, consecutive disc degeneration and the associated functional losing of the spinal segment clearly represent detrimental treatment results. In this regard, apoptosis of IVD cells has been suggested to be involved in the critical changes of the extracellular matrix. To investigate whether fractures of the vertebrae induce apoptosis in the affected IVD, disc tissue from patients (n = 17) undergoing open reduction and internal fixation of thoracolumbar spine fractures were analysed in regards to caspase activity, apoptosis-receptor expression levels and gene expression of apoptosis-regulating proteins such as Bax and Bcl-2. Healthy IVD tissue (n = 3) obtained from patients undergoing surgical resection of adjacent vertebrae were used as control samples. In contrast to healthy control IVD tissues, samples from traumatic thoracolumbar IVD showed positive TUNEL staining and a significant increase of caspase-3/7 activity. Interestingly, analyses of the initiator caspase-8 and -9 revealed significantly increased activation levels compared to control values, suggesting the coexistent activation of both the extrinsic (receptor-mediated) and intrinsic (mitochondria-mediated) apoptosis pathway. Accordingly, expression levels of the Fas receptor (FasR) mRNA were significantly increased. Although the TNF receptor I (TNFR I) was only slightly upregulated, corresponding TNFα from trauma IVD presented significantly increased mRNA expression values. Furthermore, traumatic IVD cells demonstrated significantly reduced expression of the mitochondria-bound anti-apoptotic Bcl-2, thereby maintaining baseline transcriptional levels of the pro-apoptotic Bax protein when compared to control IVD cells. Our data suggest that thoracolumbar fractures induce early caspase-dependent apoptosis in IVD cells of the affected intervertebral disc, in part, by downregulation of the anti-apoptotic protein Bcl-2 (intrinsic apoptosis pathway), as well as signalling via the death receptor complex (TNFR I and FasR).
Tài liệu tham khảo
citation_journal_title=Spine; citation_title=Mechanical initiation of intervertebral disc degeneration; citation_author=MA Adams, BJ Freeman, HP Morrison, IW Nelson, P Dolan; citation_volume=25; citation_publication_date=2000; citation_pages=1625-1636; citation_doi=10.1097/00007632-200007010-00005; citation_id=CR1
citation_journal_title=Spine; citation_title=Aging and degeneration of the human intervertebral disc; citation_author=JA Buckwalter; citation_volume=20; citation_publication_date=1995; citation_pages=1307-1314; citation_doi=10.1097/00007632-199506000-00022; citation_id=CR2
citation_journal_title=Am J Pathol; citation_title=Intervertebral disc degeneration: the role of the mitochondrial pathway in annulus fibrosus cell apoptosis induced by overload; citation_author=F Rannou, TS Lee, RH Zhou, J Chin, JC Lotz, MA Mayoux-Benhamou, JP Barbet, A Chevrot, JY Shyy; citation_volume=164; citation_publication_date=2004; citation_pages=915-924; citation_doi=10.1016/S0002-9440(10)63179-3; citation_id=CR3
citation_journal_title=Spine; citation_title=The effect of hydrostatic pressure on intervertebral disc metabolism; citation_author=WC Hutton, WA Elmer, SD Boden, S Hyon, Y Toribatake, K Tomita, GA Hair; citation_volume=24; citation_publication_date=1999; citation_pages=1507-1515; citation_doi=10.1097/00007632-199908010-00002; citation_id=CR4
citation_journal_title=Neurosurgery; citation_title=Molecular biology of degenerative disc disease; citation_author=BH Guiot, RG Fessler; citation_volume=47; citation_publication_date=2000; citation_pages=1034-1040; citation_doi=10.1097/00006123-200011000-00003; citation_id=CR5
citation_journal_title=J Biomech; citation_title=Biological response of the intervertebral disc to dynamic loading; citation_author=AJ Walsh, JC Lotz; citation_volume=37; citation_publication_date=2004; citation_pages=329-337; citation_doi=10.1016/S0021-9290(03)00290-2; citation_id=CR6
citation_journal_title=Spine; citation_title=Anti-apoptotic effects of IGF-1 and PDGF on human intervertebral disc cells in vitro; citation_author=HE Gruber, HJ Norton, ENJ Hanley; citation_volume=25; citation_publication_date=2000; citation_pages=2153-2157; citation_doi=10.1097/00007632-200009010-00002; citation_id=CR7
citation_journal_title=J Bone Joint Surg Am; citation_title=Mitochondrial involvement in fas-mediated apoptosis of human lumbar disc cells; citation_author=JB Park, JK Lee, SJ Park, KW Kim, KD Riew; citation_volume=87; citation_publication_date=2005; citation_pages=1338-1342; citation_doi=10.2106/JBJS.D.02527; citation_id=CR8
citation_journal_title=Spine; citation_title=Occurrence and regional distribution of apoptosis in scoliotic discs; citation_author=B Chen, J Fellenberg, H Wang, C Carstens, W Richter; citation_volume=30; citation_publication_date=2005; citation_pages=519-524; citation_doi=10.1097/01.brs.0000154652.96975.1f; citation_id=CR9
citation_journal_title=Spine; citation_title=Magnetic resonance classification of lumbar intervertebral disc degeneration; citation_author=CW Pfirrmann, A Metzdorf, M Zanetti, J Hodler, N Boos; citation_volume=26; citation_publication_date=2001; citation_pages=1873-1878; citation_doi=10.1097/00007632-200109010-00011; citation_id=CR10
citation_journal_title=Unfallchirurg; citation_title=[Significance of the intervertebral disk in failed reduction of surgically stabilized fractures of the truncal spine]; citation_author=P Eysel, JD Rompe, C Hopf, G Meinig; citation_volume=97; citation_publication_date=1994; citation_pages=451-457; citation_id=CR11
citation_journal_title=Unfallchirurg; citation_title=[Thoracolumbar spine fractures after conservative and surgical treatment. Dependence of correction loss on fracture level]; citation_author=S Katscher, P Verheyden, O Gonschorek, S Glasmacher, C Josten; citation_volume=106; citation_publication_date=2003; citation_pages=20-27; citation_doi=10.1007/s00113-002-0459-7; citation_id=CR12
citation_journal_title=Unfallchirurg; citation_title=[Surgical vs. conservative treatment of fractures of the thoracolumbar transition]; citation_author=H Resch, M Rabl, H Klampfer, E Ritter, P Povacz; citation_volume=103; citation_publication_date=2000; citation_pages=281-288; citation_doi=10.1007/s001130050537; citation_id=CR13
citation_journal_title=Kobe J Med Sci; citation_title=Intervertebral disc cell apoptosis by nitric oxide: biological understanding of intervertebral disc degeneration; citation_author=K Kohyama, R Saura, M Doita, K Mizuno; citation_volume=46; citation_publication_date=2000; citation_pages=283-295; citation_id=CR14
citation_journal_title=Spine; citation_title=The relationship between apoptosis of endplate chondrocytes and aging and degeneration of the intervertebral disc; citation_author=K Ariga, S Miyamoto, T Nakase, S Okuda, W Meng, K Yonenobu, H Yoshikawa; citation_volume=26; citation_publication_date=2001; citation_pages=2414-2420; citation_doi=10.1097/00007632-200111150-00004; citation_id=CR15
citation_journal_title=Spine; citation_title=Mechanical stress-induced apoptosis of endplate chondrocytes in organ-cultured mouse intervertebral discs: an ex vivo study; citation_author=K Ariga, K Yonenobu, T Nakase, N Hosono, S Okuda, W Meng, Y Tamura, H Yoshikawa; citation_volume=28; citation_publication_date=2003; citation_pages=1528-1533; citation_id=CR16
citation_journal_title=Spine; citation_title=Intervertebral disc cell death is dependent on the magnitude and duration of spinal loading; citation_author=JC Lotz, JR Chin; citation_volume=25; citation_publication_date=2000; citation_pages=1477-1483; citation_doi=10.1097/00007632-200006150-00005; citation_id=CR17
citation_journal_title=Clin Chim Acta; citation_title=Apoptosis: biochemical aspects and clinical implications; citation_author=FL Kiechle, X Zhang; citation_volume=326; citation_publication_date=2002; citation_pages=27-45; citation_doi=10.1016/S0009-8981(02)00297-8; citation_id=CR18
citation_journal_title=Faseb J; citation_title=Apoptosis in sepsis: a new target for therapeutic exploration; citation_author=C Oberholzer, A Oberholzer, M Clare-Salzler, LL Moldawer; citation_volume=15; citation_publication_date=2001; citation_pages=879-892; citation_doi=10.1096/fj.00-058rev; citation_id=CR19
citation_journal_title=J Cell Biochem; citation_title=Coordinate down-regulation of cartilage matrix gene expression in Bcl-2 deficient chondrocytes is associated with decreased SOX9 expression and decreased mRNA stability; citation_author=MD Kinkel, WEJ Horton; citation_volume=88; citation_publication_date=2003; citation_pages=941-953; citation_doi=10.1002/jcb.10442; citation_id=CR20
citation_journal_title=Spine; citation_title=Tumor necrosis factor-alpha modulates matrix production and catabolism in nucleus pulposus tissue; citation_author=CA Seguin, RM Pilliar, PJ Roughley, RA Kandel; citation_volume=30; citation_publication_date=2005; citation_pages=1940-1948; citation_doi=10.1097/01.brs.0000176188.40263.f9; citation_id=CR21
citation_journal_title=Spine; citation_title=Expression of Fas ligand and apoptosis of disc cells in herniated lumbar disc tissue; citation_author=JB Park, H Chang, KW Kim; citation_volume=26; citation_publication_date=2001; citation_pages=618-621; citation_doi=10.1097/00007632-200103150-00011; citation_id=CR22
citation_journal_title=Spine; citation_title=Expression of Fas receptor on disc cells in herniated lumbar disc tissue; citation_author=JB Park, KW Kim, CW Han, H Chang; citation_volume=26; citation_publication_date=2001; citation_pages=142-146; citation_doi=10.1097/00007632-200101150-00006; citation_id=CR23
citation_journal_title=Spine; citation_title=Internal strains in healthy and degenerated lumbar intervertebral discs; citation_author=A Tsantrizos, K Ito, M Aebi, T Steffen; citation_volume=30; citation_publication_date=2005; citation_pages=2129-2137; citation_doi=10.1097/01.brs.0000181052.56604.30; citation_id=CR24
citation_journal_title=Spine; citation_title=The elastic fiber network of the anulus fibrosus of the normal and scoliotic human intervertebral disc; citation_author=J Yu, JC Fairbank, S Roberts, JP Urban; citation_volume=30; citation_publication_date=2005; citation_pages=1815-1820; citation_doi=10.1097/01.brs.0000173899.97415.5b; citation_id=CR25
citation_journal_title=J Bone Joint Surg Br; citation_title=Intervertebral discs which cause low back pain secrete high levels of proinflammatory mediators; citation_author=JG Burke, RW Watson, D McCormack, FE Dowling, MG Walsh, JM Fitzpatrick; citation_volume=84; citation_publication_date=2002; citation_pages=196-201; citation_doi=10.1302/0301-620X.84B2.12511; citation_id=CR26