Skip to main content

Advertisement

SpringerLink
Log in

Induction of endostatin expression in meniscal fibrochondrocytes by co-culture with endothelial cells

  • Basic Science
  • Published:
Archives of Orthopaedic and Trauma Surgery Aims and scope Submit manuscript

Abstract

Introduction

The ultimate goal after meniscus damage is the preservation of the original meniscal tissue, which is often impossible due to the limited healing capacity of meniscal lesions, especially in the avascular zone. Factors produced by endothelial cells of meniscal vessels may contribute to better wound healing in vascularized zones. We therefore investigated the expression of different angiogenic factors, growth hormones and cytokines in human fibrochondrocytes and in fibrochondrocytes upon co-culture with endothelial cells, to examine mechanisms of repair of meniscal injury in more detail and to investigate the potential use of endothelial cells in co-cultures for autologous meniscal repair utilizing tissue engineering technology.

Materials and methods

Gene expression of SMAD-4, iNOS, IL-1β, VEGF, MMP-1, MMP-3, MMP-13, aggrecan, biglycan, vimentin, collagen-I, -II, -III, -IV, -VI, -X, -XVIII, angiopoietin-1, angiopoietin-2, and thrombostatin-1 were investigated in fibrochondrocytes in comparison to cells in co-culture with human umbilical vein endothelial cells (HUVEC). The expression of endostatin was enumerated in cell supernatants. A proliferation assay was used to investigate the mitotic activity of the cells.

Results

In presence of HUVEC, meniscal fibrochondrocytes expressed SMAD-4, iNOS, IL-1β, VEGF, MMP-1, MMP-3, MMP-13, aggrecan, biglycan, vimentin, collagen-I, -II, -III, -VI, and -XVIII at rates comparable to cells without HUVECs. Note that the expression of endostatin was significantly higher in the co-culture when compared to the separate fibrochondrocyte cultures and the proliferation rate of endothelial cells was significantly decreased in co-culture.

Conclusion

We conclude that the expression of the anti-angiogenic factor endostatin increased in the fibrochondrocytes. This may limit the regeneration capacities of meniscal injury in vivo.

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

Similar content being viewed by others

References

  1. Arnoczky SP, Warren RF (1983) The microvasculature of the meniscus and its response to injury. An experimental study in the dog. Am J Sports Med 11:131–141. doi:10.1177/036354658301100305

    Article  PubMed  CAS  Google Scholar 

  2. Arnoczky SP, Warren RF, Spivak JM (1988) Meniscal repair using an exogenous fibrin clot. An experimental study in dogs. J Bone Joint Surg Am 70:1209–1217

    PubMed  CAS  Google Scholar 

  3. Becker R, Pufe T, Kulow S, Giessmann N, Neumann W, Mentlein R et al (2004) Expression of vascular endothelial growth factor during healing of the meniscus in a rabbit model. J Bone Joint Surg Br 86:1082–1087. doi:10.1302/0301-620X.86B7.14349

    Article  PubMed  CAS  Google Scholar 

  4. Bluteau G, Conrozier T, Mathieu P, Vignon E, Herbage D, Mallein-Gerin F (2001) Matrix metalloproteinase-1, -3, -13 and aggrecanase-1 and -2 are differentially expressed in experimental osteoarthritis. Biochim Biophys Acta 1526:147–158

    PubMed  CAS  Google Scholar 

  5. Brocklehurst R, Bayliss MT, Maroudas A, Coysh HL, Freeman MA, Revell PA et al (1984) The composition of normal and osteoarthritic articular cartilage from human knee joints. With special reference to unicompartmental replacement and osteotomy of the knee. J Bone Joint Surg Am 66:95–106

    PubMed  CAS  Google Scholar 

  6. Ghadially FN, Lalonde JM, Wedge JH (1983) Ultrastructure of normal and torn menisci of the human knee joint. J Anat 136:773–791

    PubMed  CAS  Google Scholar 

  7. Gifford SM, Grummer MA, Pierre SA, Austin JL, Zheng J, Bird IM (2004) Functional characterization of HUVEC-CS: Ca2+ signaling, ERK 1/2 activation, mitogenesis and vasodilator production. J Endocrinol 182:485–499. doi:10.1677/joe.0.1820485

    Article  PubMed  CAS  Google Scholar 

  8. Henning CE, Lynch MA, Clark JR (1987) Vascularity for healing of meniscus repairs. Arthroscopy 3:13–18. doi:10.1016/S0749-8063(87)80004-X

    PubMed  CAS  Google Scholar 

  9. Hoberg M, Uzunmehmetoglu G, Sabic L, Reese S, Aicher WK, Rudert M (2006) Characterisation of human meniscus cells. Z Orthop Ihre Grenzgeb 144:172–178. doi:10.1055/s-2006-933364

    Article  PubMed  CAS  Google Scholar 

  10. Hofstaetter JG, Saad FA, Samuel RE, Wunderlich L, Choi YH, Glimcher MJ (2004) Differential expression of VEGF isoforms and receptors in knee joint menisci under systemic hypoxia. Biochem Biophys Res Commun 324:667–672. doi:10.1016/j.bbrc.2004.09.103

    Article  PubMed  CAS  Google Scholar 

  11. Karumanchi SA, Jha V, Ramchandran R, Karihaloo A, Tsiokas L, Chan B et al (2001) Cell surface glypicans are low-affinity endostatin receptors. Mol Cell 7:811–822. doi:10.1016/S1097-2765(01)00225-8

    Article  PubMed  CAS  Google Scholar 

  12. Lafeber FP, Vander Kraan PM, Van Roy JL, Huber-Bruning O, Bijlsma JW (1993) Articular cartilage explant culture; an appropriate in vitro system to compare osteoarthritic and normal human cartilage. Connect Tissue Res 29:287–299. doi:10.3109/03008209309016834

    Article  PubMed  CAS  Google Scholar 

  13. Nakata K, Shino K, Hamada M, Mae T, Miyama T, Shinjo H et al (2001) Human meniscus cell: characterization of the primary culture and use for tissue engineering. Clin Orthop Relat Res 391:S208–S218. doi:10.1097/00003086-200110001-00020

    Article  PubMed  Google Scholar 

  14. Nasu K, Fujisawa K, Nishida Y, Kai S, Sugano T, Miyakawa I et al (2003) Expression of collagen XVIII mRNA and protein in human umbilical vein and placenta. Reprod Fertil Dev 15:107–114. doi:10.1071/RD02067

    Article  PubMed  CAS  Google Scholar 

  15. Petersen W, Pufe T, Starke C, Fuchs T, Kopf S, Neumann W et al (2007) The effect of locally applied vascular endothelial growth factor on meniscus healing: gross and histological findings. Arch Orthop Trauma Surg 127:235–240. doi:10.1007/s00402-005-0024-2

    Article  PubMed  Google Scholar 

  16. Petersen W, Pufe T, Starke C, Fuchs T, Kopf S, Raschke M et al (2005) Locally applied angiogenic factors—a new therapeutic tool for meniscal repair. Ann Anat 187:509–519. doi:10.1016/j.aanat.2005.04.010

    Article  PubMed  CAS  Google Scholar 

  17. Petersen W, Tillmann B (1999) Structure and vascularization of the knee joint menisci. Z Orthop Ihre Grenzgeb 137:31–37

    Article  PubMed  CAS  Google Scholar 

  18. Pufe T, Petersen WJ, Miosge N, Goldring MB, Mentlein R, Varoga DJ et al (2004) Endostatin/collagen XVII—an inhibitor of angiogenesis—is expressed in cartilage and fibrocartilage. Matrix Biol 23:267–276. doi:10.1016/j.matbio.2004.06.003

    Article  PubMed  CAS  Google Scholar 

  19. Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M (2005) Anti-angiogenic effects of a nutrient mixture on human umbilical vein endothelial cells. Oncol Rep 14:1399–1404

    PubMed  Google Scholar 

  20. Scapinelli R (1968) Studies on the vasculature of the human knee joint. Acta Anat (Basel) 70:305–331

    Article  CAS  Google Scholar 

  21. Schmidt A, Addicks K, Bloch W (2004) Opposite effects of endostatin on different endothelial cells. Cancer Biol Ther 3:1162–1166

    Article  PubMed  CAS  Google Scholar 

  22. Verdonk PC, Forsyth RG, Wang J, Almqvist KF, Verdonk R, Veys EM et al (2005) Characterisation of human knee meniscus cell phenotype. Osteoarthr Cartil 13:548–560. doi:10.1016/j.joca.2005.01.010

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research has been funded in part by grants from the Deutsche Arthrose Hilfe, and the “fortuen”—programme for young researchers of the University of Tuebingen and by institutional funding.

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery and Traumatology, Hospital rechts der Isar, Technical University of Munich, Ismaninger, Strasse 22, 81675, Munich, Germany

    Maik Hoberg & Maximilian Rudert

  2. Department of Orthopaedic Surgery, University Hospital Tuebingen, Tübingen, Germany

    Edda L. Schmidt, Melanie Tuerk, Viviane Stark & Wilhelm K. Aicher

Authors
  1. Maik Hoberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Edda L. Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Melanie Tuerk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Viviane Stark
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wilhelm K. Aicher
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maximilian Rudert
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maik Hoberg.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hoberg, M., Schmidt, E.L., Tuerk, M. et al. Induction of endostatin expression in meniscal fibrochondrocytes by co-culture with endothelial cells. Arch Orthop Trauma Surg 129, 1137–1143 (2009). https://doi.org/10.1007/s00402-008-0766-8

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00402-008-0766-8

Keywords

Search

Navigation