Journal of Bone and Mineral Metabolism

, Volume 30, Issue 4, pp 400–407 | Cite as

Difference in intraosseous blood vessel volume and number in osteoporotic model mice induced by spinal cord injury and sciatic nerve resection

  • Wen-Ge Ding
  • Wei-hong Yan
  • Zhao-Xiang Wei
  • Jin-Bo Liu
Original Article

Abstract

In the present study, we examined intraosseous blood vessel parameters of the tibial metaphysis in mice using microcomputed tomography (µCT) to investigate the relationship between post-nerve-injury osteoporosis and local intraosseous blood vessel volume and number. Mice were randomly divided into groups receiving spinal cord injury (SCI), sciatic nerve resection group (NX), or intact controls (30 mice/group). Four weeks after surgery, mice were perfused with silicone and the distribution of intraosseous blood vessels analyzed by μCT. The bone density, μCT microstructure, biomechanical properties, and the immunohistochemical and biochemical indicators of angiogenesis were also measured. The SCI group showed significantly reduced tibial metaphysis bone density, μCT bone microstructure, tibial biomechanical properties, indicators of angiogenesis, and intraosseous blood vessel parameters compared to the NX group. Furthermore, the spinal cord-injured mice exhibited significantly decreased intraosseous blood vessel volume and number during the development of osteoporosis. In conclusion, these data suggest that decreased intraosseous blood vessel volume and number may play an important role in the development of post-nerve-injury osteoporosis.

Keywords

Bone mineral density Osteoporosis Spinal cord injury Sciatic nerve resection 

References

  1. 1.
    Waarsing JH, Day JS, Verhaar JA, Ederveen AG, Weinans H (2006) Bone loss dynamics result in trabecular alignment in aging and ovariectomized rats. J Orthop Res 24:926–935PubMedCrossRefGoogle Scholar
  2. 2.
    Nian H, Qin LP, Chen WS, Zhang QY, Zheng HC, Wang Y (2006) Protective effect of steroidal saponins from rhizome of Anemarrhena asphodeloides on ovariectomy-induced bone loss in rats. Acta Pharmacol Sin 27:728–734PubMedCrossRefGoogle Scholar
  3. 3.
    Jiang SD, Jiang LS, Dai LY (2006) Spinal cord injury causes more damage to bone mass, bone structure, biomechanical properties and bone metabolism than sciatic neurectomy in young rats. Osteoporos Int 17:1552–1561PubMedCrossRefGoogle Scholar
  4. 4.
    Jiang SD, Shen C, Jiang LS, Dai LY (2007) Differences of bone mass and bone structure in osteopenic rat models caused by spinal cord injury and ovariectomy. Osteoporos Int 18:743–750PubMedCrossRefGoogle Scholar
  5. 5.
    Jiang SD, Jiang LS, Dai LY (2007) Changes in bone mass, bone structure, bone biomechanical properties, and bone metabolism after spinal cord injury: a 6-month longitudinal study in growing rats. Calcif Tissue Int 80:167–175PubMedCrossRefGoogle Scholar
  6. 6.
    Liu D, Zhao CQ, Li H, Jiang SD, Jiang LS, Dai LY (2008) Effects of spinal cord injury and hindlimb immobilization on sublesional and supralesional bones in young growing rats. Bone 43:119–125PubMedCrossRefGoogle Scholar
  7. 7.
    Dauty M, Perrouin Verbe B, Maugars Y, Dubois C, Mathe JF (2000) Supralesional and sublesional bone mineral density in spinal cord-injured patients. Bone 27:305–309PubMedCrossRefGoogle Scholar
  8. 8.
    Leblanc AD, Schneider VS, Evans HJ, Engelbretson DA, Krebs JM (1990) Bone mineral loss and recovery after 17 weeks of bed rest. J Bone Miner Res 5:843–850PubMedCrossRefGoogle Scholar
  9. 9.
    Iwamoto J, Takeda T, Ichimura S, Sato Y, Yeh JK (2003) Comparative effects of orchidectomy and sciatic neurectomy on cortical and cancellous bone in young growing rats. J Bone Miner Metab 21:211–216PubMedGoogle Scholar
  10. 10.
    Geris L, Gerisch A, Sloten JV, Weiner R, Oosterwyck HV (2008) Angiogenesis in bone fracture healing: a bioregulatory model. J Theor Biol 251:137–158PubMedCrossRefGoogle Scholar
  11. 11.
    Towler DA (2007) Vascular biology and bone formation: hints from HIF. J Clin Invest 117:1477–1480PubMedCrossRefGoogle Scholar
  12. 12.
    Athanasopoulos AN, Schneider D, Keiper T, Alt V, Pendurthi UR, Liegibel UM, Sommer U, Nawroth PP, Kasperk C, Chavakis T (2007) Vascular endothelial growth factor (VEGF)-induced up-regulation of CCN1 in osteoblasts mediates proangiogenic activities in endothelial cells and promotes fracture healing. J Biol Chem 282:26746–26753PubMedCrossRefGoogle Scholar
  13. 13.
    Egrise D, Martin D, Neve P, Vienne A, Verhas M, Schoutens A (1992) Bone blood flow and in vitro proliferation of bone marrow and trabecular bone osteoblast-like cells in ovariectomized rats. Calcif Tissue Int 50:336–341PubMedCrossRefGoogle Scholar
  14. 14.
    Prisby RD, Ramsey MW, Behnke BJ, Dominguez JM 2nd, Donato AJ, Allen MR, Delp MD (2007) Aging reduces skeletal blood flow, endothelium-dependent vasodilation, and NO bioavailability in rats. J Bone Miner Res 22:1280–1288PubMedCrossRefGoogle Scholar
  15. 15.
    Dominguez JM 2nd, Prisby RD, Muller-Delp JM, Allen MR, Delp MD. Increased nitric oxide-mediated vasodilation of bone resistance arteries is associated with increased trabecular bone volume after endurance training in rats. Bone 46:813–819Google Scholar
  16. 16.
    Duvall CL, Taylor WR, Weiss D, Wojtowicz AM, Guldberg RE (2007) Impaired angiogenesis, early callus formation, and late stage remodeling in fracture healing of osteopontin-deficient mice. J Bone Miner Res 22:286–297PubMedCrossRefGoogle Scholar
  17. 17.
    Chantraine A, Nusgens B, Lapiere CM (1986) Bone remodeling during the development of osteoporosis in paraplegia. Calcif Tissue Int 38:323–327PubMedCrossRefGoogle Scholar
  18. 18.
    Jiang SD, Jiang LS, Dai LY (2007) Effects of spinal cord injury on osteoblastogenesis, osteoclastogenesis and gene expression profiling in osteoblasts in young rats. Osteoporos Int 18:339–349PubMedCrossRefGoogle Scholar
  19. 19.
    Chenu C, Serre CM, Raynal C, Burt-Pichat B, Delmas PD (1998) Glutamate receptors are expressed by bone cells and are involved in bone resorption. Bone 22:295–299PubMedCrossRefGoogle Scholar
  20. 20.
    Konttinen Y, Imai S, Suda A (1996) Neuropeptides and the puzzle of bone remodeling. State of the art. Acta Orthop Scand 67:632–639PubMedCrossRefGoogle Scholar
  21. 21.
    Jiang SD, Dai LY, Jiang LS (2006) Osteoporosis after spinal cord injury. Osteoporos Int 17:180–192PubMedCrossRefGoogle Scholar
  22. 22.
    Hunter J (2007) A treatise on the blood, inflammation, and gun-shot wounds. 1794. Clin Orthop Relat Res 458:27–34PubMedCrossRefGoogle Scholar
  23. 23.
    Geiger F, Bertram H, Berger I, Lorenz H, Wall O, Eckhardt C, Simank HG, Richter W (2005) Vascular endothelial growth factor gene-activated matrix (VEGF165-GAM) enhances osteogenesis and angiogenesis in large segmental bone defects. J Bone Miner Res 20:2028–2035PubMedCrossRefGoogle Scholar
  24. 24.
    Leach JK, Kaigler D, Wang Z, Krebsbach PH, Mooney DJ (2006) Coating of VEGF-releasing scaffolds with bioactive glass for angiogenesis and bone regeneration. Biomaterials 27:3249–3255PubMedCrossRefGoogle Scholar
  25. 25.
    Glowacki J (1998) Angiogenesis in fracture repair. Clin Orthop Relat Res S82–S89Google Scholar
  26. 26.
    Ferguson C, Alpern E, Miclau T, Helms JA (1999) Does adult fracture repair recapitulate embryonic skeletal formation? Mech Dev 87:57–66PubMedCrossRefGoogle Scholar
  27. 27.
    Yang Q, McHugh KP, Patntirapong S, Gu X, Wunderlich L, Hauschka PV (2008) VEGF enhancement of osteoclast survival and bone resorption involves VEGF receptor-2 signaling and beta3-integrin. Matrix Biol 27:589–599PubMedCrossRefGoogle Scholar
  28. 28.
    Abe M (2008) Link between osteoclastogenesis, angiogenesis and myeloma expansion. Clin Calcium 18:473–479PubMedGoogle Scholar
  29. 29.
    Hausman MR, Schaffler MB, Majeska RJ (2001) Prevention of fracture healing in rats by an inhibitor of angiogenesis. Bone 29:560–564PubMedCrossRefGoogle Scholar
  30. 30.
    Ding WG, Wei ZX, Liu JB (2011) Reduced local blood supply to the tibial metaphysis is associated with ovariectomy-induced osteoporosis in mice. Connect Tissue Res 52:25–29PubMedCrossRefGoogle Scholar
  31. 31.
    Griffith JF, Yeung DK, Tsang PH, Choi KC, Kwok TC, Ahuja AT, Leung KS, Leung PC (2008) Compromised bone marrow perfusion in osteoporosis. J Bone Miner Res 23:1068–1075PubMedCrossRefGoogle Scholar
  32. 32.
    Laroche M (2002) Intraosseous circulation from physiology to disease. Joint Bone Spine 69:262–269PubMedCrossRefGoogle Scholar
  33. 33.
    Orlic I, Borovecki F, Simic P, Vukicevic S (2007) Gene expression profiling in bone tissue of osteoporotic mice. Arh Hig Rada Toksikol 58:3–11PubMedCrossRefGoogle Scholar
  34. 34.
    Garcia-Sanz A, Rodriguez-Barbero A, Bentley MD, Ritman EL, Romero JC (1998) Three-dimensional microcomputed tomography of renal vasculature in rats. Hypertension 31:440–444PubMedCrossRefGoogle Scholar
  35. 35.
    Wietholt C, Roerig DL, Gordon JB, Haworth ST, Molthen RC, Clough AV (2008) Bronchial circulation angiogenesis in the rat quantified with SPECT and micro-CT. Eur J Nucl Med Mol Imaging 35:1124–1132PubMedCrossRefGoogle Scholar
  36. 36.
    Daghini E, Zhu XY, Versari D, Bentley MD, Napoli C, Lerman A, Lerman LO (2007) Antioxidant vitamins induce angiogenesis in the normal pig kidney. Am J Physiol Renal Physiol 293:F371–F381PubMedCrossRefGoogle Scholar
  37. 37.
    Cheung AM, Brown AS, Cucevic V, Roy M, Needles A, Yang V, Hicklin DJ, Kerbel RS, Foster FS (2007) Detecting vascular changes in tumour xenografts using micro-ultrasound and micro-ct following treatment with VEGFR-2 blocking antibodies. Ultrasound Med Biol 33:1259–1268PubMedCrossRefGoogle Scholar
  38. 38.
    Schneider P, Krucker T, Meyer E, Ulmann-Schuler A, Weber B, Stampanoni M, Muller R (2009) Simultaneous 3D visualization and quantification of murine bone and bone vasculature using micro-computed tomography and vascular replica. Microsc Res Tech 72:690–701PubMedCrossRefGoogle Scholar
  39. 39.
    Lu C, Marcucio R, Miclau T (2006) Assessing angiogenesis during fracture healing. Iowa Orthop J 26:17–26PubMedGoogle Scholar
  40. 40.
    Stefanou D, Batistatou A, Arkoumani E, Ntzani E, Agnantis NJ (2004) Expression of vascular endothelial growth factor (VEGF) and association with microvessel density in small-cell and non-small-cell lung carcinomas. Histol Histopathol 19:37–42PubMedGoogle Scholar
  41. 41.
    Des Guetz G, Uzzan B, Nicolas P, Cucherat M, Morere JF, Benamouzig R, Breau JL, Perret GY (2006) Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature. Br J Cancer 94:1823–1832PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Society for Bone and Mineral Research and Springer 2011

Authors and Affiliations

  • Wen-Ge Ding
    • 1
  • Wei-hong Yan
    • 1
  • Zhao-Xiang Wei
    • 1
  • Jin-Bo Liu
    • 1
  1. 1.Department of OrthopaedicsThird Affiliated Hospital of Suzhou UniversityChangzhouChina

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