Skip to main content
SpringerLink
Log in

Changes in vascularity of cartilage endplate of degenerated intervertebral discs in response to melatonin administration in rats

  • Basic Research
  • Published:
Neurosurgical Review Aims and scope Submit manuscript

Abstract

We carried out an experimental investigation of cartilage endplate vascularity of degenerated intervertebral discs produced by exogenous melatonin (MEL) treatment. Adult Swiss albino rats were divided into three groups: control, operated degeneration, and MEL treatment. There were five rats in each group and, using a posterior approach, cuts were made parallel to the endplates in the posterior annulus fibrosus in five consecutive intervertebral discs between the 5th and 10th vertebral segments of the rats' tails. At 8 weeks, five of these animals were treated with exogenous MEL (s.c. injection of 30 μg/100 g body weight daily for 4 weeks). In each experimental group, one animal was examined using CT scanner to study the density of the cartilage endplate of the disc. To evaluate the bone growth and vascularity of the cartilage endplate region, the animals were killed for subsequent histopathological evaluation. We found that the vascular channel counts and percentage areas from animals treated with MEL were significantly lower than from the operated degeneration animals. Accordingly, the density histogram in the MEL group showed a spike profile for both the vertebral body and the cartilage endplate, indicating an increase in the amount of higher density tissues in these regions. Our results demonstrate that the use of MEL reduces the cartilage endplate vascularity of degenerated intervertebral discs, suggesting that it may have an osteoinductive effect on bone formation. Further studies are needed to characterize fully the relevance of our findings for the treatment of disorders such as postmenopausal osteoporosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2a–c.
Fig. 3a–c.

Similar content being viewed by others

References

  1. Abdel-Wanis ME, Kawahara N, Tomita K (2001) The association of neurofibromatosis 1 and spinal deformity with primary hyperparathyroidism and osteomalacia: might melatonin have a role? J Orthop Sci 6:193–198

    Article  CAS  PubMed  Google Scholar 

  2. Aloia JF, Cohn SH, Vaswani A, Yeh JK, Yuen K, Ellis K (1985) Risk factors for postmenopausal osteoporosis. Am J Med 78:95–100

    CAS  Google Scholar 

  3. Brinckmann P, Porter RW (1994) A laboratory model of lumbar disc protrusion. Spine 19:228–235

    CAS  PubMed  Google Scholar 

  4. Bromme HJ, Morke W, Peschke D, Ebelt H, Peschke D (2000) Scavenging effect of melatonin on hydroxyl radicals generated by alloxan. J Pineal Res 29:201–108

    Article  CAS  PubMed  Google Scholar 

  5. Brzezinski A (1997) Melatonin in humans. N Engl J Med 336:186–195

    CAS  PubMed  Google Scholar 

  6. Chalkey J (1943) Methods for quantitative morphological analysis of tissue. J Natl Cancer Inst 4:47–53

    Google Scholar 

  7. Cronin AJ, Keifer JC, Davies MF, King TS, Bixler EO (2000) Melatonin secretion after surgery. Lancet 356:1244–1245

    Article  CAS  PubMed  Google Scholar 

  8. Cuzzocrea S, Costantino G, Gitto E, Mazzon E, Fulia F, Serraino I, Cordaro S, Barberi I, De Sarro A, Caputi AP (2000) Protective effects of melatonin in ischemic brain injury. J Pineal Res 29:217–227

    Article  CAS  PubMed  Google Scholar 

  9. Fauteck JD, Schmidt H, Lerchl A, Kurlemann G, Wittkowski W (1999) Melatonin in epilepsy: first results of replacement therapy and first clinical results. Biol Signals Recept 8:105–110

    Article  CAS  PubMed  Google Scholar 

  10. Fujimoto T, Nakamura T, Ikeda T, Takagi K (2000) Potent protective effects of melatonin on experimental spinal cord injury. Spine 25:769–775

    Article  CAS  PubMed  Google Scholar 

  11. Fukayama S, Tashjian AH Jr (1990) Stimulation by parathyroid hormone of 45Ca2+ uptake in osteoblast-like cells: possible involvement of alkaline phosphatase. Endocrinology 126:1941–1949

    CAS  PubMed  Google Scholar 

  12. Gitto E, Tan DX, Reiter RJ, Karbownik M, Manchester LC, Cuzzocrea S, Fulia F, Barberi I (2001) Individual and synergic antioxidative actions of melatonin: studies with vitamin E, vitamin C, glutathione and desferioxamine (desferoxamine) in rat liver homogenates. J Pharm Pharmacol 53:1393–1401

    CAS  PubMed  Google Scholar 

  13. Gordon N (2000) The therapeutics of melatonin: a paediatric perspective. Brain Dev 22:213–217

    Article  CAS  PubMed  Google Scholar 

  14. Harada A, Okuizumi H, Miyagi N, Genda E (1998) Correlation between bone mineral density and intervertebral disc degeneration. Spine 23:857–862

    Article  CAS  PubMed  Google Scholar 

  15. Holm S (1993) Pathophysiology of disc degeneration. Acta Orthop Scand 64:13–15

    PubMed  Google Scholar 

  16. Holm S, Maroudas A, Urban JPG, Selstam G, Nachemson A (1981) Nutrition of the intervertebral disc: solute transport and metabolism. Connect Tissue Res 8:101–119

    CAS  PubMed  Google Scholar 

  17. James JIP (1970) The etiology of scoliosis. J Bone Joint Surg Br 52:410–419

    CAS  PubMed  Google Scholar 

  18. Jan JE, Espezel H, Freeman RD, Fast DK (1998) Melatonin treatment of chronic sleep disorders. J Child Neurol 13:98

    CAS  PubMed  Google Scholar 

  19. Kim YS, Joo WS, Jin BK, Cho YH, Baik HH, Park VW (1998) Melatonin protects 6-OHDA-induced neuronal death of nigrostriatal dopaminergic system. Neuroreport 9:2387–2390

    CAS  PubMed  Google Scholar 

  20. Lane-Petter W, Pearson AEG (1971) The laboratory animal: principles and practice. Academic Press, London

    Google Scholar 

  21. Latorre A, Albareda J, Castiella T, Lasierra JM, Seral F (1998) Experimental model of multidirectional disc hernia in rats. Int Orthop 22:44–48

    Article  CAS  Google Scholar 

  22. Lindblom K (1952) Experimental ruptures of intervertebral disc in rat's tails. J Bone Joint Surg Am 34:123–128

    Google Scholar 

  23. Lipson SJ, Muir H (1981) Experimental intervertebral disc degeneration. Morphologic and proteoglycan changes over time. Arthritis Rheum 24:12–21

    CAS  PubMed  Google Scholar 

  24. Lissoni P, Fumagalli L, Paolorossi F, Rovelli F, Roselli MG, Maestroni GJ (1997) Anticancer neuroimmunomodulation by pineal hormones other than melatonin: preliminary phase II study of the pineal indole 5-methoxytryptophol inassociation with low-dose IL-2 and melatonin. J Biol Regul Homeost Agents 11:119–122

    CAS  PubMed  Google Scholar 

  25. Lissoni P, Rovelli F, Meregalli S, Fumagalli L, Musco F, Brivio F, Brivio O, Esposti G (1997) Melatonin as a new possible anti-inflammatory agent. J Biol Regul Homeost Agents 11:157–159

    CAS  PubMed  Google Scholar 

  26. Lissoni P, Tancini G, Barni S, Paolorossi F, Ardizzoia A, Conti A, Maestroni G (1997) Treatment of cancer chemotherapy-induced toxicity with the pineal hormone melatonin. Support Care Cancer 5:126–129

    Article  CAS  PubMed  Google Scholar 

  27. Machida M (1999) Cause of idiopathic scoliosis. Spine 24:2576–2583

    Article  CAS  PubMed  Google Scholar 

  28. Maestroni GJM (1993) The immunoendocrine role of melatonin. J Pineal Res 14:1–10

    CAS  PubMed  Google Scholar 

  29. McFadden KD, Taylor JR (1989) End plate lesions of the lumbar spine. Spine 14:867–869

    CAS  PubMed  Google Scholar 

  30. Meema S, Bunkler ML, Meema HE (1975) Preventive effect of estrogen on postmenopausal bone loss. Arch Intern Med 135:1436–1440

    Article  CAS  PubMed  Google Scholar 

  31. Mesenge C, Margaill I, Verrecchia C, Allix M, Boulu RG, Plotkine M (1998) Protective effect of melatonin in a model of traumatic brain injury in mice. J Pineal Res 25:41–46

    CAS  PubMed  Google Scholar 

  32. Nachemson A, Lewin T, Maroudas A, Freeman MAR (1970) In vitro diffusion of dye through the endplates and the annulus fibrosus of human intervertebral discs. Acta Orthop Scand 41:589–607

    CAS  PubMed  Google Scholar 

  33. Nakade O, Koyama H, Ariji H, Yajima A, Kaku T (1999) Melatonin stimulates proliferation and type I collagen synthesis in human bone cells in vitro. J Pineal Res 27:106–110

    CAS  PubMed  Google Scholar 

  34. Neufeld JH, Machado T, Margelin L (1991) Variables affecting disc size in the lumbar spine of rabbits: anesthesia, paralysis and disc injury. J Orthop Res 9:104–112

    CAS  PubMed  Google Scholar 

  35. Ostrowska Z, Kos-Kudla B, Marek B, Kajdaniuk D, Staszewicz P, Szapska B, Strzelczyk J (2002) The influence of pinealectomy and melatonin administration on the dynamic pattern of biochemical markers of bone metabolism in experimental osteoporosis in the rat. Neuroendocrinol Lett 23:104–109

    CAS  PubMed  Google Scholar 

  36. Ostrowska Z, Kos-Kudla B, Marek B, Swietochowska E, Gorski J (2001) Assessment of the relationship between circadian variations of salivary melatonin levels and type I collagen metabolism in postmenopausal obese women. Neuroendocrinol Lett 22:121–127

    CAS  PubMed  Google Scholar 

  37. Ostrowska Z, Kos-Kudla B, Swietochowska E, Marek B, Kajdaniuk D, Gorski J (2001) Assessment of the relationship between dynamic pattern of nighttime levels of melatonin and chosen biochemical markers of bone metabolism in a rat model of postmenopausal osteoporosis. Neuroendocrinol Lett 22:129–136

    CAS  PubMed  Google Scholar 

  38. Peres MFP, Seabra MLV, Zukerman E, Tufik S (2000) Cluster headache and melatonin. Lancet 355:147

    CAS  Google Scholar 

  39. Pritzker KPH (1977) Aging and degeneration in the lumbar intervertebral disc. Orthop Clin North Am 8:65–77

    Google Scholar 

  40. Reiter RJ, Calvo JR, Karbownik M, Qi W, Tan DX (2000) Melatonin and its relation to the immune system and inflammation. Ann N Y Acad Sci 917:376–386

    CAS  PubMed  Google Scholar 

  41. Reiter RJ, Tan DX, Osuna C, Gitto E (2000) Actions of melatonin in the reduction of oxidative stress. A review. J Biomed Sci 7:444–458

    CAS  PubMed  Google Scholar 

  42. Roberts S, Menage J, Urban JPG (1989) Biochemical and structural properties of the cartilage end-plate and its relation to the intervertebral disc. Spine 14:166–173

    CAS  PubMed  Google Scholar 

  43. Roth JA, Kim BG, Lin WL, Cho MI (1999) Melatonin promotes osteoblast differentiation and bone formation. J Biol Chem 274:22041–22047

    Article  CAS  PubMed  Google Scholar 

  44. Sadat-Ali M, al-Habdan I, al-Othman A (2000) Adolescent idiopathic scoliosis. Is low melatonin a cause? Joint Bone Spine 67:62–64

    CAS  PubMed  Google Scholar 

  45. Shi S, Kırk M, Kahn AJ (1996) The role of type I collagen in the regulation of the osteoblast phenotype. J Bone Miner Res 11:139–145

    Google Scholar 

  46. Shilo L, Dagan Y, Smorjik Y, Weinberg U, Dolev S, Komptel B, Shenkman L (2000) Effect of melatonin on sleep quality of COPD intensive care patients: a pilot study. Chronobiol Int 17:71–76

    Article  CAS  PubMed  Google Scholar 

  47. Silberberg R (1988) Histologic and morphometric observations on vertebral bone of aging sand rats. Spine 13:202–208

    CAS  PubMed  Google Scholar 

  48. Stokes IA, Counts DF, Frymoyer JW (1989) Experimental instability in rabbit lumbar spine. Spine 14:68–72

    CAS  PubMed  Google Scholar 

  49. Takenaka Y, Revel M, Kahan A, Amor B (1987) Experimental model of disc herniations in rats for study of nucleolytic drugs. Spine 12:556–560

    CAS  PubMed  Google Scholar 

  50. Tan DX, Manchester LC, Reiter RJ, Cabrera J, Burkhardt S, Phillip T, Gitto E, Karbownik M, Li QD (2000) Melatonin suppresses autoxidation and hydrogen peroxide-induced lipid peroxidation in monkey brain homogenate. Neuroendocrinol Lett 21:361–365

    CAS  PubMed  Google Scholar 

  51. Trueta J (1963) The role of vessels in osteogenesis. J Bone Joint Surg Am 45:402–418

    Google Scholar 

  52. Verstraeten A, Ermen HV, Haghebaert G, Nijs J, Geusens P, Dequeker J (1991) Osteoarthritis retards the development of osteoporosis: observations of coexistence of osteoarthrosis and osteoporosis. Clin Orthop 264:169–177

    PubMed  Google Scholar 

  53. Weibel ER (1979) Stereological methods. Academic Press, New York

  54. Yamada K (1962) The dynamics of experimental posture. Experimental study of intervertebral disc herniation in bipedal animals. Clin Orthop 25:20–31

    CAS  Google Scholar 

  55. Yasuma T, Makino E, Saito S, Inui M (1986) Histological development of intervertebral disc herniation. J Bone Joint Surg Am 68:1066–1072

    CAS  PubMed  Google Scholar 

  56. Yu S, Haughton VM, Sether LA, Wagner M (1988) Annulus fibrosus in bulging intervertebral disks. Radiology 169:761–763

    CAS  PubMed  Google Scholar 

  57. Zagra A, Lamartina C, Pace A, Ramondetta V, Vercellesi E (1990) Computer-assisted tomography of scoliosis operated with or without Harrington's rod. Biomechanics aspects of the fusion. Spine 15:796–802

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are indebted to Fatma Özdemir, İsmail Zonguldak, Namık Tavus, Feyzi Subaşı, and Çağlar Uz for their technical assistance and suggestions during the investigation and preparation of this article. We also thank the anonymous reviewers of Neurosurgical Review for their constructive comments and help with the manuscript. The authors indicated in the byline made substantial contributions to the following research tasks: initial conception (M.T.), design (M.T., A.U.), provision of resources (M.T., M.E.Y.), collection of data (M.T., A.U., S.U.), statistical analysis (H.Ü.), laboratory analysis and interpretation of data (M.T., A.U., S.U., H.Ü.), drafting of the manuscript (M.T., S.U.), critical revision of the manuscript for important intellectual content (M.T., A.U., H.Ü., M.E.Y.), and study supervision (M.T., M.E.Y.).

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Faculty of Medicine, Adnan Menderes University, Aydın, Turkey

    Mehmet Turgut

  2. Cumhuriyet Mahallesi, Cumhuriyet Caddesi, No:6 Daire:7, 09020, Aydın, Turkey

    Mehmet Turgut

  3. Department of Histology and Embryology, Faculty of Medicine, Ege University, İzmir, Turkey

    Serap Uslu, Ayşegül Uysal & Mine Ertem Yurtseven

  4. Department of Biostatistics, Computer Engineering, Ege University, İzmir, Turkey

    Hatice Üstün

Authors
  1. Mehmet Turgut
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Serap Uslu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ayşegül Uysal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mine Ertem Yurtseven
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hatice Üstün
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mehmet Turgut.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Turgut, M., Uslu, S., Uysal, A. et al. Changes in vascularity of cartilage endplate of degenerated intervertebral discs in response to melatonin administration in rats. Neurosurg Rev 26, 133–138 (2003). https://doi.org/10.1007/s10143-003-0259-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10143-003-0259-8

Keywords

Search

Navigation