DOI QR코드

DOI QR Code

Notochordal Cells Influence Gene Expression of Inflammatory Mediators of Annulus Fibrosus Cells in Proinflammatory Cytokines Stimulation

  • Moon, Hong-Joo (Department of Neurosurgery, College of Medicine, Korea University) ;
  • Joe, Hoon (Department of Neurosurgery, College of Medicine, Korea University) ;
  • Kwon, Taek-Hyun (Department of Neurosurgery, College of Medicine, Korea University) ;
  • Choi, Hye-Kyoung (Department of Neurosurgery, College of Medicine, Korea University) ;
  • Park, Youn-Kwan (Department of Neurosurgery, College of Medicine, Korea University) ;
  • Kim, Joo-Han (Department of Neurosurgery, College of Medicine, Korea University)
  • 투고 : 2010.05.03
  • 심사 : 2010.06.29
  • 발행 : 2010.07.28

초록

Objective : Notochordal cells in the intervertebral disc interact with nucleus pulposus (NP) cells and support the maintenance of disc homeostasis by regulation of matrix production. However, the influence of notochordal cells has not been evaluated in the annulus fibrosus (AF), which is the primary pain generator in the disc. We hypothesized that the notochordal cell has the capacity to modulate inflammatory mediators secreted by AF cells secondary to stimulation. Methods : Notochordal and AF cells were isolated from adult New Zealand white rabbits. AF pellets were cultured with notochordal cell clusters or in notochordal cell-conditioned media (NCCM) for 24 or 48 hours with proinflammatory cytokines at varying concentrations. Gene expression in AF pellets were assayed for nitric oxide synthase (iNOS), cyclo-oxygenase (COX)-2, and interleukin (IL)-6 by real time reverse transcriptase polymerase chain reaction (RT-PCR). Results : AF pellet in NCCM significantly decreased the iNOS and COX-2 messenger ribonucleic acid (mRNA) levels compared to AF pellets alone and AF pellets with notochordal cells (p < 0.05). AF pellet resulted in dose-dependent iNOS and COX-2 expression in response to IL-$1{\beta}$, stimulation, demonstrating that 1 ng/ml for 24 hours yielded a maximal response. AF pellet in NCCM significantly decreased the expression of iNOS and COX-2 in response to 1ng/ml IL-$1{\beta}$, stimulation at 24 hours (p < 0.05). There was no difference in IL-6 expression compared to AF pellets alone or AF pellets with notochordal cell clusters. Conclusion : We conclude that soluble factors from notochordal cells mitigate the gene expression of inflammatory mediators in stimulated AF, as expected after annular injury, suggesting that notochordal cells could serve as a novel therapeutic approach in symptomatic disc development.

키워드

과제정보

연구 과제 주관 기관 : Korea Research Foundation

참고문헌

  1. Aguiar DJ, Johnson SL, Oegema TR : Notochordal cells interact with nucleus pulposus cells : regulation of proteoglycan synthesis. Exp Cell Res 246 : 129-137, 1999 https://doi.org/10.1006/excr.1998.4287
  2. Baer AE, Wang JY, Kraus VB, Setton LA : Collagen gene expression and mechanical properties of intervertebral disc cell-alginate cultures. J Orthop Res 19 : 2-10, 2001 https://doi.org/10.1016/S0736-0266(00)00003-6
  3. Biyani A, Andersson GB : Low back pain : pathophysiology and management. J Am Acad Orthop Surg 12 : 106-115, 2004
  4. Boos N, Weissbach S, Rohrbach H, Weiler C, Spratt KF, Nerlich AG : Classification of age-related changes in lumbar intervertebral discs : 2002 Volvo Award in basic science. Spine (Phila Pa 1976) 27 : 2631-2644, 2002 https://doi.org/10.1097/00007632-200212010-00002
  5. Burke JG, Watson RW, McCormack D, Dowling FE, Walsh MG, Fitzpatrick JM : Intervertebral discs which cause low back pain secrete high levels of proinflammatory mediators. J Bone Joint Surg Br 84 : 196-201, 2002 https://doi.org/10.1302/0301-620X.84B2.12511
  6. Erwin WM, Ashman K, O'Donnel P, Inman R : Nucleus pulposus notochord cells secrete connective tissue growth factor and up-regulate proteoglycan expression by intervertebral disc chondrocytes. Arthritis Rheum 54 : 3859-3867, 2006 https://doi.org/10.1002/art.22258
  7. Erwin WM, Inman RD : Notochord cells regulate intervertebral disc chondrocyte proteoglycan production and cell proliferation. Spine (Phila Pa 1976) 31 : 1094-1099, 2006 https://doi.org/10.1097/01.brs.0000216593.97157.dd
  8. Ghosh P, Taylor TK, Braund KG : The variation of the glycosaminoglycans of the canine intervertebral disc with ageing. I. Chondrodystrophoid breed. Gerontology 23 : 87-98, 1977 https://doi.org/10.1159/000212177
  9. Humzah MD, Soames RW : Human intervertebral disc : structure and function. Anat Rec 220 : 337-356, 1988 https://doi.org/10.1002/ar.1092200402
  10. Kang JD, Georgescu HI, McIntyre-Larkin L, Stefanovic-Racic M, Donaldson WF 3rd, Evans CH : Herniated lumbar intervertebral discs spontaneously produce matrix metalloproteinases, nitric oxide, interleukin-6, and prostaglandin E2. Spine (Phila Pa 1976) 21 : 271-277, 1996 https://doi.org/10.1097/00007632-199602010-00003
  11. Kim JH, Studer RK, Sowa GA, Vo NV, Kang JD : Activated macrophage- like THP-1 cells modulate anulus fibrosus cell production of inflammatory mediators in response to cytokines. Spine (Phila Pa 1976) 33 : 2253-2259, 2008 https://doi.org/10.1097/BRS.0b013e318182c35f
  12. Kim JH, Studer RK, Vo NV, Sowa GA, Kang JD : p38 MAPK inhibition selectively mitigates inflammatory mediators and VEGF production in AF cells co-cultured with activated macrophage-like THP-1 cells. Osteoarthritis Cartilage 17 : 1662-1669, 2009 https://doi.org/10.1016/j.joca.2009.06.004
  13. Masuda K, Miyabayashi T, Meachum SH, Eurell TE : Proliferation of canine intervertebral disk chondrocytes in three-dimensional alginate microsphere culture. J Vet Med Sci 64 : 79-82, 2002 https://doi.org/10.1292/jvms.64.79
  14. Minami T, Okuda-Ashitaka E, Hori Y, Sakuma S, Sugimoto T, Sakimura K, et al. : Involvement of primary afferent C-fibres in touchevoked pain (allodynia) induced by prostaglandin E2. Eur J Neurosci 11 : 1849-1856, 1999 https://doi.org/10.1046/j.1460-9568.1999.00602.x
  15. Namkoong S, Lee SJ, Kim CK, Kim YM, Chung HT, Lee H, et al. : Prostaglandin E2 stimulates angiogenesis by activating the nitric oxide/cGMP pathway in human umbilical vein endothelial cells. Exp Mol Med 37 : 588-600, 2005 https://doi.org/10.1038/emm.2005.72
  16. Okuma M, Mochida J, Nishimura K, Sakabe K, Seiki K : Reinsertion of stimulated nucleus pulposus cells retards intervertebral disc degeneration : an in vitro and in vivo experimental study. J Orthop Res 18 : 988-997, 2000 https://doi.org/10.1002/jor.1100180620
  17. Peng B, Hao J, Hou S, Wu W, Jiang D, Fu X, et al. : Possible pathogenesis of painful intervertebral disc degeneration. Spine (Phila Pa 1976) 31 : 560-566, 2006 https://doi.org/10.1097/01.brs.0000201324.45537.46
  18. Rand N, Reichert F, Floman Y, Rotshenker S : Murine nucleus pulposus-derived cells secrete interleukins-1-beta, -6, and -10 and granulocyte-macrophage colony-stimulating factor in cell culture. Spine 22 : 2598-2601; discussion 2602, 1997 https://doi.org/10.1097/00007632-199711150-00002
  19. Stevens JW, Kurriger GL, Carter AS, Maynard JA : CD44 expression in the developing and growing rat intervertebral disc. Dev Dyn 219 : 381-390, 2000 https://doi.org/10.1002/1097-0177(2000)9999:9999<::AID-DVDY1060>3.0.CO;2-P
  20. Takahashi H, Suguro T, Okazima Y, Motegi M, Okada Y, Kakiuchi T : Inflammatory cytokines in the herniated disc of the lumbar spine. Spine (Phila Pa 1976) 21 : 218-224, 1996 https://doi.org/10.1097/00007632-199601150-00011
  21. Urban JP, Roberts S : Development and degeneration of the intervertebral discs. Mol Med Today 1 : 329-335, 1995 https://doi.org/10.1016/S1357-4310(95)80032-8
  22. Walmsley R : The development and growth of the intervertebral disc. Edinb Med J 60 : 341-364, 1953
  23. Weiler C, Nerlich AG, Bachmeier BE, Boos N : Expression and distribution of tumor necrosis factor alpha in human lumbar intervertebral discs : a study in surgical specimen and autopsy controls. Spine (Phila Pa 1976) 30 : 44-53; discussion 54, 2005 https://doi.org/10.1097/01.brs.0000174529.07959.c0
  24. Yoshida M, Nakamura T, Sei A, Kikuchi T, Takagi K, Matsukawa A : Intervertebral disc cells produce tumor necrosis factor alpha, interleukin-1beta, and monocyte chemoattractant protein-1 immediately after herniation : an experimental study using a new hernia model. Spine (Phila Pa 1976) 30 : 55-61, 2005 https://doi.org/10.1097/01.brs.0000149194.17891.bf

피인용 문헌

  1. Neural Mechanisms of Discogenic Back Pain: How Does Nerve Growth Factor Play a Key Role? vol.8, pp.2, 2011, https://doi.org/10.14245/kjs.2011.8.2.83
  2. Dynamic pressurization induces transition of notochordal cells to a mature phenotype while retaining production of important patterning ligands from development vol.15, pp.5, 2010, https://doi.org/10.1186/ar4302
  3. Inflammatory Mediators in Intervertebral Disk Degeneration and Discogenic Pain vol.3, pp.3, 2013, https://doi.org/10.1055/s-0033-1347299
  4. Notochordal Cell-Derived Therapeutic Strategies for Discogenic Back Pain vol.3, pp.3, 2010, https://doi.org/10.1055/s-0033-1350053
  5. Matrix Degradative Enzymes and Their Inhibitors during Annular Inflammation : Initial Step of Symptomatic Intervertebral Disc Degeneration vol.55, pp.5, 2010, https://doi.org/10.3340/jkns.2014.55.5.237
  6. Different concentrations of 17β-estradiol modulates apoptosis induced by interleukin-1β in rat annulus fibrosus cells vol.10, pp.5, 2014, https://doi.org/10.3892/mmr.2014.2514
  7. * Coculture with Partial Digestion Notochordal Cell-Rich Nucleus Pulposus Tissue Activates Degenerative Human Nucleus Pulposus Cells vol.23, pp.15, 2017, https://doi.org/10.1089/ten.tea.2016.0428