Advertisement

Immunohistochemical examination in arthrofibrosis of the knee joint

  • Hermann O. MayrEmail author
  • Fanny F. Fassbender
  • Wolf C. Prall
  • Florian Haasters
  • Anke Bernstein
  • Amelie Stoehr
Knee Revision Surgery
  • 33 Downloads

Abstract

Introduction

Arthrofibrosis (AF) is the result of increased cell proliferation and synthesis of matrix proteins (collagen I, III, and VI). Especially after invasive knee surgery, e.g., ligament reconstruction or knee replacement, abnormal fibroblast proliferation with pathological periarticular fibrosis can be observed leading to severely limited joint motion. The pathogenesis of AF is currently not fully understood. The present work aims to determine pathogenic factors.

Materials and methods

A descriptive, histological and immunohistochemical comparative study was performed on tissue samples of 14 consecutive patients undergoing arthrolysis for joint stiffness due to AF. Seven human autopsy specimens served as control. Samples were stained for expression of relevant markers such as CD68, α-smooth muscle actin (ASMA), beta-catenin, BMP-2 and examined for the histological grade of AF (cell-rich versus cell-poor) and compared to a control. Furthermore, a microscopic evaluation of the samples for cell differentiation and number was performed.

Results

Tissue sections of cell-rich fibrosis showed a significantly higher expression of CD68 compared to the control with less than 10% of CD68 positive cells (p = 0.002). In cell-poor fibrosis no statistically significant difference was obvious (p = 0.228). Expression of ASMA in synovia, vessels, cell-rich and cell-poor fibrosis showed median values of 2.00 in the AF group and 1.75 in the control. Both groups differed significantly (p = 0.003). AF tissue showed a significantly difference in expression of β-catenin (p < 0.001) compared to the control. The overall difference between AF and control group in expression of BMP-2 was also statistically significant (p = 0.002).

Conclusions

Expression of CD68, ASMA, beta-catenin and BMP-2 is significantly increased in AF tissue samples. Based on presented findings, histological evaluation and immunohistochemical assessment of CD68, ASMA, β-catenin and BMP-2 expression may proof useful to diagnose AF and to analyze AF activity.

Keywords

Arthrofibrosis Knee Immunohistochemical examination CD68 ASMA Beta-catenin BMP-2 

Notes

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest with regard to the current study.

References

  1. 1.
    Bosch U (2002) Arthrofibrosis. Der Orthopäde 31(8):785–790CrossRefGoogle Scholar
  2. 2.
    Shelbourne KD, Patel DV, Martini DJ (1996) Classification and management of arthrofibrosis of the knee after anterior cruciate ligament reconstruction. Am J Sports Med 24(6):857–862CrossRefGoogle Scholar
  3. 3.
    Harner CD, Irrgang JJ, Paul J, Dearwater S, Fu FH (1992) Loss of motion after anterior cruciate ligament reconstruction. Am J Sports Med 20(5):499–506CrossRefGoogle Scholar
  4. 4.
    Said S, Christainsen SE, Faunoe P, Lund B, Lind M (2011) Outcome of surgical treatment of arthrofibrosis following ligament reconstruction. Knee Surg Sports Traumatol Arthrosc 19(10):1704–1708CrossRefGoogle Scholar
  5. 5.
    Mayr HO, Stöhr A (2014) Arthroscopic treatment of arthrofibrosis after ACL reconstruction. Local and generalized arthrofibrosis. Oper Orthop Traumatol 26(1):7–18CrossRefGoogle Scholar
  6. 6.
    Watson RS, Gouze E, Levings PP, Bush ML, Kay JD, Jorgensen MS, Dacanay EA, Reith JW, Wright TW, Ghivizzani SC (2010) Gene delivery of TGF-beta1 induces arthrofibrosis and chondrometaplasia of synovium in vivo. Lab Invest 90(11):1615–1627CrossRefGoogle Scholar
  7. 7.
    Ruppert M, Theiss C, Knöβ P, Kendoff D, Krukemeyer MG, Schröder N, Brand-Saberi B, Gehrke T, Krenn V (2013) Histopathological, immunohistochemical criteria and confocal laser-scanning data of arthrofibrosis. Pathol Res Pract 209(11):681–688CrossRefGoogle Scholar
  8. 8.
    MacDonald BT, Tamai K, He X (2009) Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 17(1):9–26CrossRefGoogle Scholar
  9. 9.
    Beyer C, Schramm A, Akhmetshina A, Dees C, Kireva T, Gelse K, Sonnylal S, de Crombrugghe B, Taketo MM, Distler O, Schett G, Distler JH (2012) beta-catenin is a central mediator of pro-fibrotic Wnt signaling in systemic sclerosis. Ann Rheum Dis 71(5):761–767CrossRefGoogle Scholar
  10. 10.
    Freeman TA, Parvizi J, Dela Valle CJ, Steinbeck MJ (2010) Mast cells and hypoxia drive tissue metaplasia and heterotopic ossification in idiopathic arthrofibrosis after total knee arthroplasty. Fibrogenes Tissue Repair 3:17CrossRefGoogle Scholar
  11. 11.
    Pfitzner T, Geissler S, Duda G, Perka C, Matziolis G (2012) Increased BMP expression in arthrofibrosis after TKA. Knee Surg Sports Traumatol Arthrosc 20(9):1803–1808CrossRefGoogle Scholar
  12. 12.
    Pfitzner T, Röhner E, Krenn V, Perka C, Matziolis G (2012) BMP-2 dependent increase of soft tissue density in arthrofibrotic TKA. Open Orthop J 6:199–203CrossRefGoogle Scholar
  13. 13.
    Riley EH, Lane JM, Urist MR, Lyons KM, Lieberman JR (1996) Bone morphogenetic protein-2: biology and applications. Clin Orthop Relat Res 324:39–46CrossRefGoogle Scholar
  14. 14.
    Mucke J, Hoyer A, Brinks R, Bleck E, Pauly T, Schneider M, Vordenbäumen S (2016) Inhomogeneity of immune cell composition in the synovial sublining: linear mixed modelling indicates differences in distribution and spatial decline of CD68 + macrophages in osteoarthritis and rheumatoid arthritis. Arthritis Res Ther 18:170CrossRefGoogle Scholar
  15. 15.
    Bresnihan B, Pontifex E, Thurlings RM, Vinkenoog M, El-Gabalawy H, Fearon U, Fitzgerald O, Gerlag DM, Rooney T, van de Sande MG, Veale D, Vos K, Tak PP (2009) Synovial tissue sublining CD68 expression is a biomarker of therapeutic response in rheumatoid arthritis clinical trials: consistency across centers. J Rheumatol 36(8):1800–1802CrossRefGoogle Scholar
  16. 16.
    Faust I, Traut P, Nolting F, Petschallies J, Neumann E, Kunisch E, Kuhn J, Knabbe C, Hendig D (2015) Human xylosyltransferases–mediators of arthrofibrosis? New pathomechanistic insights into arthrofibrotic remodeling after knee replacement therapy. Sci Rep 5:12537CrossRefGoogle Scholar
  17. 17.
    Unterhauser FN, Bosch U, Zeichen J, Weiler A (2004) Alpha-smooth muscle actin containing contractile fibroblastic cells in human knee arthrofibrosis tissue. Winner of the AGA-DonJoy Award 2003. Arch Orthop Trauma Surg Nov 124(9):585–591CrossRefGoogle Scholar
  18. 18.
    Wynn TA (2007) Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases. J Clin Invest Mar 117(3):524–529 (Review) CrossRefGoogle Scholar
  19. 19.
    Hartsock A, Nelson WJ (2008) Adherens and tight junctions: structure, function and connections to the actin cytoskeleton. Biochim Biophys Acta Mar 1778(3):660–669. (Review) CrossRefGoogle Scholar
  20. 20.
    Bowley E, O’Gorman DB, Gan BS (2007) Beta-catenin signaling in fibroproliferative disease. J Surg Res Mar 138(1):141–150CrossRefGoogle Scholar
  21. 21.
    Chilosi M, Caliò A, Rossi A, Gilioli E, Pedica F, Montagna L, Pedron S, Confalonieri M, Doglioni C, Ziesche R, Grubinger M, Mikulits W, Poletti V (2017) Epithelial to mesenchymal transition-related proteins ZEB1, β-catenin, and β-tubulin-III in idiopathic pulmonary fibrosis. Mod Pathol 30(1):26–38CrossRefGoogle Scholar
  22. 22.
    Degreef I, De Smet L, Sciot R, Cassiman JJ, Tejpar S (2009) Beta-catenin overexpression in Dupuytren’s disease is unrelated to disease recurrence. Clin Orthop Relat Res Mar 467(3):838–845CrossRefGoogle Scholar
  23. 23.
    Ferenc T, Wroński JW, Kopczyński J, Kulig A, Sidor M, Stalińska L, Dziki A, Sygut J (2009) Analysis of APC, alpha-, beta-catenins, and N-cadherin protein expression in aggressive fibromatosis (desmoid tumor). Pathol Res Pract 205(5):311–324CrossRefGoogle Scholar
  24. 24.
    Chemel M, Brion R, Segaliny AI, Lamora A, Charrier C, Brulin B, Maugars Y, Le Goff B, Heymann D, Verrecchia F (2017) Bone morphogenetic protein 2 and transforming growth factor β1 inhibit the expression of the proinflammatory cytokine IL-34 in rheumatoid arthritis synovial fibroblasts. Am J Pathol 187(1):156–162CrossRefGoogle Scholar
  25. 25.
    Robin BN, Chaput CD, Zeitouni S, Rahm MD, Zerris VA, Sampson HW (2010) Cytokine-mediated inflammatory reaction following posterior cervical decompression and fusion associated with recombinant human bone morphogenetic protein-2: a case study. Spine (Phila Pa 1976) 35(23):E1350–E1354CrossRefGoogle Scholar
  26. 26.
    Zara JN, Siu RK, Zhang X, Shen J, Ngo R, Lee M, Li W, Chiang M, Chung J, Kwak J, Wu BM, Ting K, Soo C (2011) High doses of bone morphogenetic protein 2 induce structurally abnormal bone and inflammation in vivo. Tissue Eng Part A 17(9–10):1389–1399CrossRefGoogle Scholar
  27. 27.
    Ries MD, Badalamente M (2000) Arthrofibrosis after total knee arthroplasty. Clin Orthop Relat Res 380:177–183CrossRefGoogle Scholar
  28. 28.
    Freeman TA, Parvizi J, Della Valle CJ, Steinbeck MJ (2009) Reactive oxygen and nitrogen species induce protein and DNA modifications driving arthrofibrosis following total knee arthroplasty. Fibrogenes Tissue Repair 2(1):5CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Orthopaedics and TraumatologyAlbert Ludwig University of FreiburgFreiburgGermany
  2. 2.Department of Knee, Hip and Shoulder Surgery, Schön Clinik Munich-HarlachingAcademic Teaching Hospital of the Paracelsus Private Medical University SalzburgSalzburgAustria
  3. 3.Department of General, Trauma and Reconstructive SurgeryMunich University Hospital LMUMunichGermany
  4. 4.OCM Clinic MunichMunichGermany

Personalised recommendations