Skip to main content
SpringerLink
Log in

Expression of vascular endothelial growth factor and angiogenesis in patellar tendon grafts in the early phase after anterior cruciate ligament reconstruction

  • Knee
  • Published:
Knee Surgery, Sports Traumatology, Arthroscopy Aims and scope

Abstract

The aim of this study was to clarify vascular endothelial growth factor (VEGF) expression and angiogenesis in the patellar tendon (PT) autograft in the early phase after anterior cruciate ligament (ACL) reconstruction using a rabbit model. The right knees of 30 Japanese white rabbits underwent ACL reconstruction using the medial third of the PT complex. We evaluated the grafted tendon at 1, 2, 3, 4, and 8 weeks after ACL reconstruction by immunohistology for proliferating cell nuclear antigen, VEGF, and CD31, which is a marker for vascular endothelial cells. At week 1 , few cells were observed at the midsubstance of the grafted tendon. A number of proliferating cells were observed at the surface area of the PT graft 2 weeks after graft transplantation, while no vessel formation was observed in the graft at the same time. VEGF was highly expressed 2–3 weeks postoperatively. Vessel formation in the PT graft increased with time from 3 to 8 weeks after ACL reconstruction. The rates of proliferating cells and VEGF-expressing cells decreased with time from 3 to 8 weeks. This study has suggested that VEGF is involved in the graft remodeling process particularly at the early phase after ACL reconstruction.

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. 2
Fig. 3

Similar content being viewed by others

References

  1. Amiel D, Kleiner JB, Roux RD, Harwood FL, Akeson WH (1986) The phenomenon of “ligamentization”: anterior cruciate ligament reconstruction with autogenous patellar tendon. J Orthop Res 4:162–172

    Article  PubMed  CAS  Google Scholar 

  2. Ankoma-Sey V, Wang Y, Dai Z (2000) Hypoxic stimulation of vascular endothelial growth factor expression in activated rat hepatic stellate cells. Hepatology 31:141–148

    Article  PubMed  CAS  Google Scholar 

  3. Arnoczky SP, Tarvin GB, Marshall JL (1982) Anterior cruciate ligament replacement using patellar tendon. An evaluation of graft revascularization in the dog. J Bone Joint Surg Am 64:217–224

    PubMed  CAS  Google Scholar 

  4. Ballock RT, Woo SLY, Lyon RM, Hollis JM, Akenson WH (1989) Use of patellar tendon autograft for anterior cruciate ligament reconstruction in the rabbit: a long-term histologic and biomechanical study. J Orthop Res 7:474–485

    Article  PubMed  CAS  Google Scholar 

  5. Bidder M, Towler DA, Gelberman RH, Boyer MI (2000) Expression of mRNA for vascular endothelial growth factor at the repair site of healing canine flexor tendon. J Orthop Res 18:247–252

    Article  PubMed  CAS  Google Scholar 

  6. Corral CJ, Siddiqui A, Wu L, Farrell CL, Lyons D, Mustoe TA (1999) Vascular endothelial growth factor is more important than basic fibroblastic growth factor during ischemic wound healing. Arch Surg 134:200–205

    Article  PubMed  CAS  Google Scholar 

  7. Clancy WG Jr, Narechania RG, Rosenberg TD, Gmeiner JG, Wisnefske DD, Lange TA. (1981) Anterior and posterior cruciate ligament reconstruction in rhesus monkeys. J Bone Joint Surg Am 63:1270–1284

    PubMed  Google Scholar 

  8. Delay BS, McGrath BE, Mindell ER (2002) Observations on a retrieved patellar tendon autograft used to reconstruct the anterior cruciate ligament. A case report. J Bone Joint Surg Am 84A:1433–1438

    Google Scholar 

  9. Fox SB, Leek RD, Weekes MP, Whitehouse RM, Gatter KC, Harris AL (1995) Quantitation and prognostic value of breast cancer angiogenesis: comparison of microvessel density, Chalkley count, and computer image analysis. J Pathol 177:275–283

    Article  PubMed  CAS  Google Scholar 

  10. Jin KL, Mao XO, Greenberg DA (2000) Vascular endothelial growth factor: direct neuroprotective effect in in vitro ischemia. Proc Natl Acad Sci USA 97:10242–10247

    Article  PubMed  CAS  Google Scholar 

  11. .Kleiner JB, Amiel D, Roux RD, Akeson WH (1986) Origin of replacement cells for the anterior cruciate ligament autograft. J Orthop Res 4:466–474

    Article  PubMed  CAS  Google Scholar 

  12. Kleiner JB, Amiel D, Harwood FL, Akeson WH (1989) Early histologic, metabolic, and vascular assessment of anterior cruciate ligament autografts. J Orthop Res 7:235–242

    Article  PubMed  CAS  Google Scholar 

  13. Marti HH, Risau W (1998) Systemic hypoxia changes the organ-specific distribution of vascular endothelial growth factor and its receptors. Proc Natl Acad Sci USA 95:15809–15814

    Article  PubMed  CAS  Google Scholar 

  14. Nagashima M, Yoshino S, Ishiwata T, Asano G (1995) Role of vascular endothelial growth factor in angiogenesis of rheumatoid arthritis. J Rheumatol 22:1624–1630

    PubMed  CAS  Google Scholar 

  15. Olfert IM, Breen EC, Mathieu-Costello O, Wagner PD (2001) Skeletal muscle capillarity and angiogenic mRNA levels after exercise training in normoxia and chronic hypoxia. J Appl Physiol 91:1176–1184

    PubMed  CAS  Google Scholar 

  16. Ozaki NK, Beharry KD, Nishihara KC, Akmal Y, Ang JG, Sheikh R, Modanlou HD (2002) Regulation of retinal vascular endothelial growth factor and receptors in rabbits exposed to hyperoxia. Invest Ophthalmol Vis Sci 43:1546–1557

    PubMed  Google Scholar 

  17. Paleolog EM, Young S, Stark AC, McCloskey RV, Feldmann M, Maini RN (1998) Modulation of angiogenic vascular endothelial growth factor by tumor necrosis factor alpha and interleukin-1 in rheumatoid arthritis. Arthritis Rheum 41:1258–1265

    Article  PubMed  CAS  Google Scholar 

  18. Petersen W, Unterhauser F, Pufe T, Zantop T, Sudkamp NP, Weiler A (2003) The angiogenic peptide vascular endothelial growth factor (VEGF) is expressed during the remodeling of free tendon grafts in sheep. Arch Orthop Trauma Surg 123:168–174

    PubMed  Google Scholar 

  19. Pufe T, Petersen W, Tillmann B, Mentlein R (2001) Splice variants VEGF121 and VEGF189 of vascular endothelial growth factor are expressed in osteoarthritic cartilage. Arthritis Rheum 44:1082–1088

    Article  PubMed  CAS  Google Scholar 

  20. Pufe T, Petersen W, Tillmann B, Mentlein R (2001) Detection of the vascular endothelial growth factor in fetal, degenerative and normal human tendons. Virchows Arch 439:579–585

    Article  PubMed  CAS  Google Scholar 

  21. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascitis fluid. Science 219:983–985

    Article  PubMed  CAS  Google Scholar 

  22. Uchida S, Sakai A, Kudo H, Otomo H, Watanuki M, Tanaka M, Nagashima M, Nakamura T (2003) Vascular endothelial growth factor is expressed along with its receptors during the healing process of bone and bone marrow after drill-hole injury in rats. Bone 32:491–501

    Article  PubMed  CAS  Google Scholar 

  23. Uchida H, Tohyama H, Nagashima K, Matsumoto H, Toyama Y, Yasuda K (2005) Stress deprivation simultaneously induces over-expression of interleukin-1beta, tumor necrosis factor-alpha, and transforming growth factor-beta in fibroblasts and mechanical deterioration of the tissue in the patellar tendon. J Biomech 38:791–798

    Article  PubMed  Google Scholar 

  24. Ushiyama T, Chano T, Inoue K, Matsusue Y (2003) Cytokine production in the infrapatellar fat pad: another source of cytokines in knee synovial fluids. Ann Rheum Dis 62:108–112

    Article  PubMed  CAS  Google Scholar 

  25. Zhang F, Lei MP, Oswald TM, Pang Y, Blain B, Cai ZW, Lineaweaver WC (2003) The effect of vascular endothelial growth factor on the healing of ischaemic skin wounds. Br J Plast Surg 56:334–341

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Sports Medicine and Joint Reconstruction Surgery, Hokkaido University School of Medicine, Kita-15 Nishi-7 Kita-ku, Sapporo, 060-8638, Tokyo, Japan

    T. Yoshikawa, H. Tohyama & K. Yasuda

  2. Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan

    T. Yoshikawa, H. Enomoto, H. Matsumoto & Y. Toyama

Authors
  1. T. Yoshikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Tohyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Enomoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Y. Toyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K. Yasuda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. Tohyama.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yoshikawa, T., Tohyama, H., Enomoto, H. et al. Expression of vascular endothelial growth factor and angiogenesis in patellar tendon grafts in the early phase after anterior cruciate ligament reconstruction. Knee Surg Sports Traumatol Arthr 14, 804–810 (2006). https://doi.org/10.1007/s00167-006-0051-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00167-006-0051-8

Keywords

Search

Navigation