Acta Chir Orthop Traumatol Cech. 2015; 82(1):67-75 | DOI: 10.55095/achot2015/009

Low Expression of TLR-1, -2, -4 a IL-2, -2R, -10, -10R and TGFb1 in Pseudosynovial Tissue Collected at Revision Total Knee Arthroplasty for Aseptic LooseningOriginal papers

T. Tománková1, E. Kriegová1, R. Fillerová1, P. Lužná2, J. Ehrmann2, J. Gallo3,*
1 Ústav imunologie, Lékařská fakulta UP v Olomouci
2 Ústav histologie a embryologie, Lékařská fakulta UP v Olomouci
3 Ortopedická klinika LF UP v Olomouci a FN Olomouc

PURPOSE OF THE STUDY:
Aseptic loosening (AL) and periprosthetic osteolysis (PPOL) in total hip (THA) and knee (TKA) arthroplasty are linked to an inflammatory process initiated by wear debris released from artificial joints. There is still limited information about the contribution of Toll-like receptors (TLRs) and distinct regulatory cytokines to AL/PPOL in both joints.

METHODS:
In this study, we investigated mRNA expression of TLR-1,-2,-4 and cytokines/receptors (IL-2,-2R,-10,-10R, TGFb1) in pseudosynovial tissue obtained from 55 patients with aseptically failed THAs/TKAs and 37 control patients with hip/knee primary osteoarthritis (OA) using quantitative RT-PCR. Immunohistochemical staining was used to detect the corresponding proteins. Non-parametric Kruskal-Wallis and Mann-Whitney tests were used to determine differences between the patient groups.

RESULTS:
When comparing expression profiles between patients with aseptically failed THA and TKA, higher amounts of TLR-1,-2,-4 and IL-2R mRNA transcripts were detected in THA patients. The mRNA expression of studied molecules (TLR-1,-2,-4, IL-2, IL-10, IL-2R, IL-10R, TGFb1) did not differ between THA and OA hip tissues. Lower mRNA expression of TLR-1,-2,-4, IL-10, and IL-10R was detected in TKA when compared to control knee OA. Similar mRNA profiles of IL-2, IL-2R, and TGFb1 were observed in TKA and knee OA. Using immunohistochemistry, we detected low expression of TLR-1 protein in failed THA/TKA, whereas TLR-2 protein levels were higher in TKA/THA patients than in OA controls. High individual variability in TLR-4 protein levels was detected among patients with aseptically loosened THA and TKA. IL-10 protein levels were similar in THA and TKA patient subgroups and control subjects, whereas IL-10R protein level was higher in failed TKAs and OA controls than in THAs. No difference in IL-2 protein levels was detected between patients with THA/TKA and those with OA.

DISCUSSION:
Our data indicate close similarity between the expression patterns in aseptically failed THA and TKA. However, certain differences were observed which also suggest unique pathways associated with the end-stage of aseptic loosening in THA and TKA. For instance, differences in the size, shape and load of polyethylene particles between THA and TKA could play some role. The composition of THA and TKA and differences in terms of mechanical forces might also be involved.

CONCLUSIONS:
This is the first study comparing the gene expression profile of a particular set of innate immunity regulatory molecules between tissues from aseptically failed THA and TKA. Low expression of TLR-1,-2,-4 and cytokines/receptors (IL-2, IL-2R, IL-10, IL-10R, and TGFb1) was observed in pseudosynovial tissues obtained from aseptically failed THAs and TKAs. Higher amount of TLR transcripts was detected in THA as compared to TKA. These findings indicate certain differences in the mechanism of aseptic loosening occurring at the site of THA and TKA. Further research is warranted.

Keywords: aseptic loosening, periprosthetic osteolysis, total hip arthroplasty, total knee arthroplasty, gene expression, immunohistochemistry, TLRs, cytokines, IL-2, IL-10, TGFb1

Published: February 1, 2015  Show citation

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Tománková T, Kriegová E, Fillerová R, Lužná P, Ehrmann J, Gallo J. Low Expression of TLR-1, -2, -4 a IL-2, -2R, -10, -10R and TGFb1 in Pseudosynovial Tissue Collected at Revision Total Knee Arthroplasty for Aseptic Loosening. Acta Chir Orthop Traumatol Cech. 2015;82(1):67-75. doi: 10.55095/achot2015/009. PubMed PMID: 25748664.
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References

  1. ANDERSON, J. M., RODRIGUES, A., CHANG D. T.: Foreign body reaction to biomaterials. Semin. Immunol., 20: 86-100, 2008. Go to original source... Go to PubMed...
  2. ASSMANN, G., KASCH, R., HOFER, A., SCHULZ, A. P., KAYSER, R., LAHM, A., MERK, H., FLESSA, S.: An economic analysis of aseptic revision hip arthroplasty: calculation of partial hospital costs in relation to reimbursement. Arch. Orthop. Trauma Surg., 134: 413-420, 2014. Go to original source... Go to PubMed...
  3. ENGH, G. A., AMMEEN, D. J.: Bone loss with revision total knee arthroplasty: defect classification and alternatives for reconstruction. Instr. Course Lect., 48: 167-175, 1999.
  4. GALLO, J., GOODMAN, S. B., KONTTINEN, Y. T., RASKA, M.: Particle disease: biologic mechanisms of periprosthetic osteolysis in total hip arthroplasty. Innate Immun., 19: 213-224, 2013. Go to original source... Go to PubMed...
  5. GALLO, J., KOLAR, M., DENDIS, M., LOVECKOVA, Y., SAUER, P., ZAPLETALOVA, J., KOUKALOVA, D.: Culture and PCR analysis of joint fluid in the diagnosis of prosthetic joint infection. New Microbiol., 31: 97-104, 2008.
  6. GALLO, J., LOSTAK, J., LANGOVA, K.: Long-term survival of the uncemented Balgrist total hip replacement cup. Int. Orthop., 37: 1449-1456, 2013. Go to original source... Go to PubMed...
  7. GALLO, J., MRAZEK, F., PETREK, M.: Variation in cytokine genes can contribute to severity of acetabular osteolysis and risk for revision in patients with ABG 1 total hip arthroplasty: a genetic association study. BMC Med. Genet., 10: 109, 2009. Go to original source... Go to PubMed...
  8. GENTZSCH, C., KAISER, E., PLUTAT, J., SELLCKAU, R., WODTKE, J., DELLING, G.: cDNA array approach to cytokine expression profile of aseptic loosened hip arthroplasty. Pathologe, 23: 373-378, 2002. Go to original source... Go to PubMed...
  9. GREEN, T. R., FISCHER, J., STONE, M., WROBLEWSKI, B. M., INGHAM, E.: Polyethylene particles of a 'critical size' are necessary for the induction of cytokines by macrophages in vitro. Biomaterials, 19: 2297-2302, 1998. Go to original source... Go to PubMed...
  10. HOFMANN, S. R., ROSEN-WOLFF, A., TSOKOS, G. C., HEDRICH, C. M.: Biological properties and regulation of IL-10 related cytokines and their contribution to autoimmune disease and tissue injury. Clin. Immunol., 143: 116-127, 2012. Go to original source... Go to PubMed...
  11. ILLGEN, R. L., 2nd, FORSYTHE, T. M, PIKE, J. W., LAURENT, M. P, BLANCHARD, C. R.: Highly crosslinked vs conventional polyethylene particles - an in vitro comparison of biologic activities. J. Arthroplasty, 23:721-731, 2008. Go to original source... Go to PubMed...
  12. IYER, S. S., CHENG, G.: Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Crit. Rev. Immunol., 32: 23-63, 2012. Go to original source... Go to PubMed...
  13. KASAGI, S., CHEN, W.: TGF-beta1 on osteoimmunology and the bone component cells. Cell Biosci.,3: 4, 2013. Go to original source... Go to PubMed...
  14. KONTTINEN, Y. T., PAJARINEN, J.: Adverse reactions to metal-on-metal implants. Nat. Rev. Rheumatol., 9: 5-6, 2013. Go to original source... Go to PubMed...
  15. KONTTINEN, Y. T., WARIS, V., XU, J. W., JIRANEK, W. A., SORSA, T., VIRTANEN, I., SANTAVIRTA, S.: Transforming growth factor-beta 1 and 2 in the synovial-like interface membrane between implant and bone in loosening of total hip arthroplasty. J. Rheumatol., 24: 694-701, 1997.
  16. KRIEGOVA, E., ARAKELYAN, A., FILLEROVA, R., ZATLOUKAL, J., MRAZEK, F., NAVRATILOVA, Z., KOLEK, V., DU BOIS, R. M., PETREK, M.: PSMB2 and RPL32 are suitable denominators to normalize gene expression profiles in bronchoalveolar cells. BMC Mol. Biol., 9: 69, 2008. Go to original source... Go to PubMed...
  17. LAHDEOJA, T., PAJARINEN, J., KOURI, V. P., SILLAT, T., SALO, J., KONTTINEN, Y. T.: Toll-like receptors and aseptic loosening of hip endoprosthesis-a potential to respond against danger signals? J. Orthop. Res., 28: 184-190, 2010. Go to original source... Go to PubMed...
  18. LI, T. F., SANTAVIRTA, S., WARIS, V., LASSUS, J., LINDROOS, L., XU, J. W., VIRTANEN, I., KONTTINEN, Y. T.: No lymphokines in T-cells around loosened hip prostheses. Acta Orthop. Scand., 72: 241-247, 2001. Go to original source... Go to PubMed...
  19. LIAO, W., LIN, J. X., LEONARD, W. J.: Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy. Immunity, 38: 13-25, 2013. Go to original source... Go to PubMed...
  20. LIN, T. H., TAMAKI, Y., PAJARINEN, J., WATERS, H. A., WOO, D. K., YAO, Z., GOODMAN, S. B.: Chronic inflammation in biomaterial-induced periprosthetic osteolysis: NF-kappaB as a therapeutic target. Acta Biomater., 10: 1-10, 2014. Go to original source... Go to PubMed...
  21. LOHMANN, C. H., DEAN, D. D., KOSTER, G., CASASOLA, D., BUCHHORN, G. H., FINK, U., SCHWARTZ, Z., BOYAN, B. D.: Ceramic and PMMA particles differentially affect osteoblast phenotype. Biomaterials, 23: 1855-1863, 2002. Go to original source... Go to PubMed...
  22. MABREY, J. D., AFSAR-KESHMIRI, A., ENGH, G. A., SYCHTERZ, C. J., WIRTH, M. A., ROCKWOOD, C. A., AGRAWAL, C. M.: Standardized analysis of UHMWPE wear particles from failed total joint arthroplasties. J. Biomed Mater. Res., 63: 475-483, 2002. Go to original source... Go to PubMed...
  23. MAITRA, R., CLEMENT, C. C., SCHARF, B., CRISI, G. M., CHITTA, S., PAGET, D., PURDUE, P. E., COBELLI, N., SANTAMBROGIO, L.: Endosomal damage and TLR2 mediated inflammasome activation by alkane particles in the generation of aseptic osteolysis. Mol. Immunol., 47: 175-184, 2009. Go to original source... Go to PubMed...
  24. MATZINGER, P.: An innate sense of danger. Ann. N Y Acad. Sci., 961: 341-342, 2002. Go to original source... Go to PubMed...
  25. MORAWIETZ, L., GEHRKE, T., FROMMELT, L., GRATZE, P., BOSIO, A., MOLLER, J., GERSTMAYER, B., KRENN, V.: Differential gene expression in the periprosthetic membrane: lubricin as a new possible pathogenetic factor in prosthesis loosening. Virchows Arch., 443: 57-66, 2003. Go to original source... Go to PubMed...
  26. NABAE, M., INOUE, K., USHIYAMA, T., HUKUDA, S.: Gene expressions of antiinflammatory mediators in THR retrieved interfacial membranes. Acta Orthop. Scand., 70: 149-154, 1999. Go to original source... Go to PubMed...
  27. NICH, C., TAKAKUBO, Y., PAJARINEN, J., AINOLA, M., SALEM, A., SILLAT, T., RAO, A. J., RASKA, M., TAMAKI, Y., TAKAGI, M., KONTTINEN, Y. T., GOODMAN, S. B., GALLO, J.: Macrophages-Key cells in the response to wear debris from joint replacements. J. Biomed. Mater. Res. A., 101: 3033-3045, 2013. Go to original source... Go to PubMed...
  28. PEARL, J. I., MA, T., IRANI, A. R., HUANG, Z., ROBINSON, W. H., SMITH, R. L., GOODMAN, S. B.: Role of the Toll-like receptor pathway in the recognition of orthopedic implant wear-debris particles. Biomaterials, 32: 5535-5542, 2011. Go to original source... Go to PubMed...
  29. POLLOCK, D., SYCHTERZ, C. J., ENGH, C. A.: A clinically practical method of manually assessing polyethylene liner thickness. J. Bone Jt Surg., 83-A: 1803-1809, 2001. Go to original source... Go to PubMed...
  30. REUVEN, E. M., FINK, A., SHAI, Y.: Regulation of innate immune responses by transmembrane interactions: lessons from the TLR family. Biochim. Biophys. Acta, 1838: 1586-1593, 2014. Go to original source... Go to PubMed...
  31. SABOKBAR, A., ITONAGA, I., SUN, S. G., KUDO, O., ATHANASOU, N. A.: Arthroplasty membrane-derived fibroblasts directly induce osteoclast formation and osteolysis in aseptic loosening. J. Orthop. Res., 23: 511-519, 2005. Go to original source... Go to PubMed...
  32. SALEH, K. J., HOLTZMAN, J., GAFNI, A., SALEH, L., DAVIS, A., RESIG, S., GROSS, A. E.: Reliability and intraoperative validity of preoperative assessment of standardized plain radiographs in predicting bone loss at revision hip surgery. J. Bone Jt Surg., 83-A: 1040-1046, 2001. Go to original source... Go to PubMed...
  33. SHANBHAG, A. S., KAUFMAN, A. M., HAYATA, K., RUBASH, H. E.: Assessing osteolysis with use of high-throughput protein chips. J. Bone Jt Surg., 89-A: 1081-1089, 2007. Go to original source... Go to PubMed...
  34. TAKACOVA, S., SLANY, R., BARTKOVA, J., STRANECKY, V., DOLEZEL, P., LUZNA, P., BARTEK, J., DIVOKY, V.: DNA damage response and inflammatory signaling limit the MLL-ENL-induced leukemogenesis in vivo. Cancer Cell., 21: 517-531, 2012. Go to original source... Go to PubMed...
  35. TAKAGI, M., TAMAKI, Y., HASEGAWA, H., TAKAKUBO, Y., KONTTINEN, L., TIAINEN, V. M., LAPPALAINEN, R., KONTTINEN, Y. T., SALO, J.: Toll-like receptors in the interface membrane around loosening total hip replacement implants. J. Biomed. Mater. Res. A., 81: 1017-1026, 2007. Go to original source... Go to PubMed...
  36. TAMAKI, Y., TAKAKUBO, Y., GOTO, K., HIRAYAMA, T., SASAKI, K., KONTTINEN, Y. T., GOODMAN, S. B., TAKAGI, M.: Increased expression of toll-like receptors in aseptic loose periprosthetic tissues and septic synovial membranes around total hip implants. J. Rheumatol., 36: 598-608, 2009. Go to original source... Go to PubMed...
  37. VALLADARES, R. D., NICH, C., ZWINGENBERGER, S., LI, C., SWANK, K. R., GIBON, E., RAO, A. J., YAO, Z., GOODMAN, S. B.: Toll-like receptors-2 and 4 are overexpressed in an experimental model of particle-induced osteolysis. J. Biomed. Mater. Res. A., 102: 3004-3011, 2014. Go to original source... Go to PubMed...
  38. WANG, C. T, LIN, Y. T., CHIANG, B. L., LEE, S. S., HOU, S. M.: Over-expression of receptor activator of nuclear factor-kappaB ligand (RANKL), inflammatory cytokines, and chemokines in periprosthetic osteolysis of loosened total hip arthroplasty. Biomaterials, 31: 77-82, 2010. Go to original source... Go to PubMed...