Skip to main content

Advertisement

SpringerLink
Log in

Alteration of the RANKL/RANK/OPG System in Periprosthetic Osteolysis with Septic Loosening

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

The pathogenesis of periprosthetic osteolysis with septic loosening remains incompletely understood. The purpose of this study was to investigate whether expression of the RANKL/RANK/OPG system is altered in septic interface membranes (SIMs). Seventeen cases with a SIM, 26 cases with an aseptic interface membrane (AIM), and 12 cases with a normal synovium (NS) were assessed. Scanning and transmission electron microscopy (SEM and TEM, respectively) were used to observe the microscopic morphology of three tissue conditions. Differences in RANKL, RANK, and OPG expression at the mRNA level were assessed by real-time quantitative PCR, and differences at the protein level were assessed by immunohistochemical staining and Western blotting. SEM showed wear debris widely distributed on the AIM surface, and TEM showed Bacillus activity in the SIM. RANKL expression and the RANKL/OPG ratio were significantly increased in SIMs. Imbalance in the RANKL/RANK/OPG system is related to periprosthetic osteolysis with septic loosening but is not the only possible pathogenic mechanism.

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
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Abbreviations

RANKL:

Receptor activator of nuclear factor-κB ligand

RANK:

Receptor activator of nuclear factor-κB

OPG:

Osteoprotegerin

SIMs:

Septic interface membranes

AIM:

Aseptic interface membrane

NS:

Normal synovium

SEM:

Scanning electron microscopy

TEM:

Transmission electron microscopy

THA:

Total hip arthroplasty

PJI:

Periprosthetic joint infection

rTHA:

Revision total hip arthroplasty

OCs:

Osteoclasts

OCPs:

Osteoclasts precursors

MCSF:

Macrophage colony-stimulating factor

TLRs:

Toll-like receptors

References

  1. Learmonth, I.D., C. Young, and C. Rorabeck. 2007. The operation of the century: Total hip replacement. Lancet 370(9597): 1508–1519.

    Article  PubMed  Google Scholar 

  2. Parvizi, J., B. Adeli, B. Zmistowski, C. Restrepo, and A.S. Greenwald. 2012. Management of periprosthetic joint infection: the current knowledge: AAOS exhibit selection. Journal of Bone and Joint Surgery (American) 94(14): e104.

    Article  Google Scholar 

  3. Goodman, S.B., E. Gibon, and Z. Yao. 2013. The basic science of periprosthetic osteolysis. Instructional Course Lectures 62: 201–206.

    PubMed Central  PubMed  Google Scholar 

  4. Pajarinen, J., E. Cenni, L. Savarino, E. Gomez-Barrena, Y. Tamaki, M. Takagi, J. Salo, and Y.T. Konttinen. 2010. Profile of toll-like receptor-positive cells in septic and aseptic loosening of total hip arthroplasty implants. Journal of Biomedical Materials Research. Part A 94(1): 84–92.

    Article  PubMed  CAS  Google Scholar 

  5. Maoz G, Phillips M, Bosco J, Slover J, Stachel A, Inneh I, and Iorio R. 2014. The Otto Aufranc award: Modifiable versus nonmodifiable risk factors for infection after hip arthroplasty. Clinical Orthopaedics and Related Research.

  6. Meehan, J.P., B. Danielsen, S.H. Kim, A.A. Jamali, and R.H. White. 2014. Younger age is associated with a higher risk of early periprosthetic joint infection and aseptic mechanical failure after total knee arthroplasty. Journal of Bone and Joint Surgery (American) 96(7): 529–535.

    Article  Google Scholar 

  7. Tsung JD, Rohrsheim JA, Whitehouse SL, Wilson MJ, and Howell JR. 2014. Management of periprosthetic joint infection after total hip arthroplasty using a custom made articulating spacer (CUMARS); the Exeter experience. The Journal of Arthroplasty.

  8. Mandelin, J., T.F. Li, M. Liljestrom, M.E. Kroon, R. Hanemaaijer, S. Santavirta, and Y.T. Konttinen. 2003. Imbalance of RANKL/RANK/OPG system in interface tissue in loosening of total hip replacement. Journal of Bone and Joint Surgery (British) 85(8): 1196–1201.

    Article  CAS  Google Scholar 

  9. Chen, D., X. Zhang, Y. Guo, S. Shi, X. Mao, X. Pan, and T. Cheng. 2012. MMP-9 inhibition suppresses wear debris-induced inflammatory osteolysis through downregulation of RANK/RANKL in a murine osteolysis model. International Journal of Molecular Medicine 30(6): 1417–1423.

    PubMed  Google Scholar 

  10. Kim, K.J., S. Kotake, N. Udagawa, H. Ida, M. Ishii, I. Takei, T. Kubo, and M. Takagi. 2001. Osteoprotegerin inhibits in vitro mouse osteoclast formation induced by joint fluid from failed total hip arthroplasty. Journal of Biomedical Materials Research 58(4): 393–400.

    Article  PubMed  CAS  Google Scholar 

  11. Masui, T., S. Sakano, Y. Hasegawa, H. Warashina, and N. Ishiguro. 2005. Expression of inflammatory cytokines, RANKL and OPG induced by titanium, cobalt-chromium and polyethylene particles. Biomaterials 26(14): 1695–1702.

    Article  PubMed  CAS  Google Scholar 

  12. Wei, X., X. Zhang, M.J. Zuscik, M.H. Drissi, E.M. Schwarz, and R.J. O’Keefe. 2005. Fibroblasts express RANKL and support osteoclastogenesis in a COX-2-dependent manner after stimulation with titanium particles. Journal of Bone and Mineral Research 20(7): 1136–1148.

    Article  PubMed  CAS  Google Scholar 

  13. Pioletti, D.P., and A. Kottelat. 2004. The influence of wear particles in the expression of osteoclastogenesis factors by osteoblasts. Biomaterials 25(27): 5803–5808.

    Article  PubMed  CAS  Google Scholar 

  14. Lacey, D.L., E. Timms, H.L. Tan, M.J. Kelley, C.R. Dunstan, T. Burgess, R. Elliott, A. Colombero, G. Elliott, S. Scully, et al. 1998. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93(2): 165–176.

    Article  PubMed  CAS  Google Scholar 

  15. Yasuda, H., N. Shima, N. Nakagawa, K. Yamaguchi, M. Kinosaki, S. Mochizuki, A. Tomoyasu, K. Yano, M. Goto, A. Murakami, et al. 1998. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proceedings of the National Academy of Sciences of the United States of America 95(7): 3597–3602.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  16. Hsu, H., D.L. Lacey, C.R. Dunstan, I. Solovyev, A. Colombero, E. Timms, H.L. Tan, G. Elliott, M.J. Kelley, I. Sarosi, et al. 1999. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proceedings of the National Academy of Sciences of the United States of America 96(7): 3540–3545.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  17. Quinn, J.M., J. Elliott, M.T. Gillespie, and T.J. Martin. 1998. A combination of osteoclast differentiation factor and macrophage-colony stimulating factor is sufficient for both human and mouse osteoclast formation in vitro. Endocrinology 139(10): 4424–4427.

    Article  PubMed  CAS  Google Scholar 

  18. Simonet, W.S., D.L. Lacey, C.R. Dunstan, M. Kelley, M.S. Chang, R. Luthy, H.Q. Nguyen, S. Wooden, L. Bennett, T. Boone, et al. 1997. Osteoprotegerin: A novel secreted protein involved in the regulation of bone density. Cell 89(2): 309–319.

    Article  PubMed  CAS  Google Scholar 

  19. Hofbauer, L.C., C.A. Kuhne, and V. Viereck. 2004. The OPG/RANKL/RANK system in metabolic bone diseases. Journal of Musculoskeletal & Neuronal Interactions 4(3): 268–275.

    CAS  Google Scholar 

  20. Achermann, Y., M. Vogt, M. Leunig, J. Wust, and A. Trampuz. 2010. Improved diagnosis of periprosthetic joint infection by multiplex PCR of sonication fluid from removed implants. Journal of Clinical Microbiology 48(4): 1208–1214.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Norton, A.J., S. Jordan, and P. Yeomans. 1994. Brief, high-temperature heat denaturation (pressure cooking): A simple and effective method of antigen retrieval for routinely processed tissues. Journal of Pathology 173(4): 371–379.

    Article  PubMed  CAS  Google Scholar 

  22. Xavier, L.L., G.G. Viola, A.C. Ferraz, C. Da Cunha, J.M. Deonizio, C.A. Netto, and M. Achaval. 2005. A simple and fast densitometric method for the analysis of tyrosine hydroxylase immunoreactivity in the substantia nigra pars compacta and in the ventral tegmental area. Brain Research. Brain Research Protocols 16(1–3): 58–64.

    Article  PubMed  CAS  Google Scholar 

  23. Wang, C.J., Z.G. Zhou, A. Holmqvist, H. Zhang, Y. Li, G. Adell, and X.F. Sun. 2009. Survivin expression quantified by Image-Pro Plus compared with visual assessment. Applied Immunohistochemistry & Molecular Morphology 17(6): 530–535.

    Article  CAS  Google Scholar 

  24. Hofbauer, L.C., and M. Schoppet. 2004. Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. JAMA 292(4): 490–495.

    Article  PubMed  CAS  Google Scholar 

  25. Xu, J., M.D. Kauther, J. Hartl, and C. Wedemeyer. 2010. Effects of alpha-calcitonin gene-related peptide on osteoprotegerin and receptor activator of nuclear factor-kappaB ligand expression in MG-63 osteoblast-like cells exposed to polyethylene particles. Journal of Orthopaedic Surgery and Research 5: 83.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Horiki, M., T. Nakase, A. Myoui, N. Sugano, T. Nishii, T. Tomita, T. Miyaji, and H. Yoshikawa. 2004. Localization of RANKL in osteolytic tissue around a loosened joint prosthesis. Journal of Bone and Mineral Metabolism 22(4): 346–351.

    Article  PubMed  CAS  Google Scholar 

  27. Zhang, L., T.H. Jia, A.C. Chong, L. Bai, H. Yu, W. Gong, P.H. Wooley, and S.Y. Yang. 2010. Cell-based osteoprotegerin therapy for debris-induced aseptic prosthetic loosening on a murine model. Gene Therapy 17(10): 1262–1269.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. Zhang, T., H. Yu, W. Gong, L. Zhang, T. Jia, P.H. Wooley, and S.Y. Yang. 2009. The effect of osteoprotegerin gene modification on wear debris-induced osteolysis in a murine model of knee prosthesis failure. Biomaterials 30(30): 6102–6108.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  29. Bori, G., E. Munoz-Mahamud, S. Garcia, C. Mallofre, X. Gallart, J. Bosch, E. Garcia, J. Riba, J. Mensa, and A. Soriano. 2011. Interface membrane is the best sample for histological study to diagnose prosthetic joint infection. Modern Pathology 24(4): 579–584.

    Article  PubMed  Google Scholar 

  30. Tohtz, S.W., M. Muller, L. Morawietz, T. Winkler, and C. Perka. 2010. Validity of frozen sections for analysis of periprosthetic loosening membranes. Clinical Orthopaedics and Related Research 468(3): 762–768.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Tamaki, Y., Y. Takakubo, K. Goto, T. Hirayama, K. Sasaki, Y.T. Konttinen, S.B. Goodman, and M. Takagi. 2009. Increased expression of toll-like receptors in aseptic loose periprosthetic tissues and septic synovial membranes around total hip implants. Journal of Rheumatology 36(3): 598–608.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was funded in part by the Natural Science Foundation of Hunan Province, China (Grant No. 12JJ2055), the Hunan Provincial Innovation Foundation for Postgraduates (Grant No. 2012B091), and the Science and Technology Planning Project of Hunan Province (Grant No. 2011FJ6085).

Competing Interests

The authors declare that they have no competing interests.

Authors’ Contributions

LW and YH conceived of the study and drafted the manuscript. LW, ZD, JX, HL, and CL prepared experimental samples. LW, ZD, HL, and CL carried out the experiments. LW and JX performed the statistical analysis. LW, YH, ZD, and JX participated in study design and helped to draft the manuscript. All authors read and approved the final manuscript.

Author information

Authors and Affiliations

  1. Department of Orthopaedics, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, People’s Republic of China

    Long Wang, Zixun Dai, Jie Xie, Hao Liao, Cheng Lv & Yihe Hu

Authors
  1. Long Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zixun Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jie Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hao Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cheng Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yihe Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yihe Hu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, L., Dai, Z., Xie, J. et al. Alteration of the RANKL/RANK/OPG System in Periprosthetic Osteolysis with Septic Loosening. Inflammation 39, 218–227 (2016). https://doi.org/10.1007/s10753-015-0241-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-015-0241-y

KEY WORDS

Search

Navigation