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Mechanism of action of genicular artery embolization in a rabbit model of knee osteoarthritis

  • Interventional
  • Published:
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Abstract

Objectives

To establish a rabbit osteoarthritis model for genicular artery embolization (GAE) experiments and to investigate the cellular mechanism of action of this novel procedure for interventional radiologists.

Methods

Rabbit knee osteoarthritis was surgically modeled by anterior cruciate ligament transection and medial partial meniscectomy of the bilateral hindlimbs followed by 10 weeks of incubation. Rabbits exhibiting synovitis on magnetic resonance imaging were randomly divided into two groups: the bilateral GAE group and the control (sham procedure) group. Four weeks later, the rabbits’ mobility (moving time, sec/10 min) and the histopathological features of each knee were assessed, and inter-group differences were evaluated using Student’s t-test and ordinal/linear logistic models with generalized estimating equations.

Results

Osteoarthritis modeling and endovascular procedures were successful in 15 of 20 rabbits (8 and 7 in the GAE and control groups, respectively). There was no significant difference in moving times between the two groups (p = .958). The degree of structural cartilage damage was similar in both groups (p = .780). However, the synovial proliferation (p = .016), synovial hypertrophy (p < .001), and villous hyperplasia of the synovial stroma (p = .002) scores were significantly lower in the GAE group than in the control group. The CD3+ cell density (p = .018) and CD3 + cell-infiltrated area (p = .019) were also significantly lower in the GAE group than in the control group.

Conclusion

GAE can limit inflammatory processes in the synovium of osteoarthritis-affected knees.

Key Points

  • Surgical transection of the anterior cruciate ligament and medial partial meniscectomy of rabbit knees provides a useful animal model for research of genicular artery embolization.

  • Osteoarthritic knees treated by genicular artery embolization showed milder synovial proliferation (p = .016), synovial hypertrophy (p < .001), and villous hyperplasia of the synovial stroma (p = .002) than the untreated knees.

  • Osteoarthritic knees treated by genicular artery embolization presented lower CD3+ cell density (p = .018) and CD3+ cell-infiltrated area (p = .019) in the synovium than the untreated knees.

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Abbreviations

GAE:

Genicular artery embolization

H&E:

Hematoxylin-and-eosin

IHC:

Immunohistochemistry

IL:

Interleukin

NSAID:

Non-steroidal anti-inflammatory drug

OARSI:

Osteoarthritis Research Society International

SD:

Standard deviation

TNFα:

Tumor necrosis factor-α

References

  1. Sharma L (2021) Osteoarthritis of the Knee. N Engl J Med 384:51–59

    Article  CAS  Google Scholar 

  2. Cui A, Li H, Wang D, Zhong J, Chen Y, Lu H (2020) Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine 29-30:100587

    Article  Google Scholar 

  3. Bannuru RR, Osani MC, Vaysbrot EE et al (2019) OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage 27:1578–1589

    Article  CAS  Google Scholar 

  4. Okuno Y, Korchi AM, Shinjo T, Kato S (2015) Transcatheter arterial embolization as a treatment for medial knee pain in patients with mild to moderate osteoarthritis. Cardiovasc Intervent Radiol 38:336–343

    Article  Google Scholar 

  5. Okuno Y, Korchi AM, Shinjo T, Kato S, Kaneko T (2017) Midterm clinical outcomes and MR imaging changes after transcatheter arterial embolization as a treatment for mild to moderate radiographic knee osteoarthritis resistant to conservative treatment. J Vasc Interv Radiol 28:995–1002

    Article  Google Scholar 

  6. Lee SH, Hwang JH, Kim DH et al (2019) Clinical outcomes of transcatheter arterial embolisation for chronic knee pain: mild-to-moderate versus severe knee osteoarthritis. Cardiovasc Intervent Radiol 42:1530–1536

    Article  Google Scholar 

  7. Bagla S, Piechowiak R, Hartman T, Orlando J, Del Gaizo D, Isaacson A (2020) Genicular artery embolization for the treatment of knee pain secondary to osteoarthritis. J Vasc Interv Radiol 31:1096–1102

    Article  Google Scholar 

  8. Choi JW, Ro DH, Chae HD et al (2020) The value of preprocedural MR imaging in genicular artery embolization for patients with osteoarthritic knee pain. J Vasc Interv Radiol 31:2043–2050

    Article  Google Scholar 

  9. Landers S, Hely R, Page R et al (2020) Genicular artery embolization to improve pain and function in early-stage knee osteoarthritis-24-month pilot study results. J Vasc Interv Radiol 31:1453–1458

    Article  Google Scholar 

  10. Little MW, Gibson M, Briggs J et al (2021) Genicular artEry embolizatioN in patiEnts with oSteoarthrItiS of the Knee (GENESIS) using permanent microspheres: interim analysis. Cardiovasc Intervent Radiol 44:931–940

    Article  CAS  Google Scholar 

  11. van Zadelhoff TA, Okuno Y, Bos PK et al (2021) Association between baseline osteoarthritic features on MR imaging and clinical outcome after genicular artery embolization for knee osteoarthritis. J Vasc Interv Radiol 32:497–503

    Article  Google Scholar 

  12. Ahmed O, Block J, Mautner K et al (2021) Percutaneous management of osteoarthritis in the knee: proceedings from the Society of Interventional Radiology Research Consensus Panel. J Vasc Interv Radiol 32:919 e911–919 e916

    Article  Google Scholar 

  13. Goldman DT, Piechowiak R, Nissman D, Bagla S, Isaacson A (2018) Current concepts and future directions of minimally invasive treatment for knee pain. Curr Rheumatol Rep 20:54

    Article  Google Scholar 

  14. Kuyinu EL, Narayanan G, Nair LS, Laurencin CT (2016) Animal models of osteoarthritis: classification, update, and measurement of outcomes. J Orthop Surg Res 11:19

    Article  Google Scholar 

  15. Lampropoulou-Adamidou K, Lelovas P, Karadimas EV et al (2014) Useful animal models for the research of osteoarthritis. Eur J Orthop Surg Traumatol 24:263–271

    Article  Google Scholar 

  16. Peterfy CG, Guermazi A, Zaim S et al (2004) Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis. Osteoarthr Cartil 12:177–190

    Article  CAS  Google Scholar 

  17. Kigata T, Horikawa Y, Shibata H (2021) Arterial branching pattern of the rabbit femoral artery. Anat Sci Int 96:273–285

    Article  Google Scholar 

  18. Laverty S, Girard CA, Williams JM, Hunziker EB, Pritzker KP (2010) The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the rabbit. Osteoarthr Cartil 18(Suppl 3):S53–S65

    Article  Google Scholar 

  19. Bankhead P, Loughrey MB, Fernandez JA et al (2017) QuPath: open source software for digital pathology image analysis. Sci Rep 7:16878

    Article  Google Scholar 

  20. Fedchenko N, Reifenrath J (2014) Different approaches for interpretation and reporting of immunohistochemistry analysis results in the bone tissue - a review. Diagn Pathol 9:221

    Article  Google Scholar 

  21. Arifin WN, Zahiruddin WM (2017) Sample size calculation in animal studies using resource equation approach. Malays J Med Sci 24:101–105

    Google Scholar 

  22. Hindso L, Riis RGC, Holmich P et al (2021) Current status of trans-arterial embolization in pain management of musculoskeletal inflammatory conditions - an evidence-based review. Cardiovasc Intervent Radiol 44:1699–1708

    Article  Google Scholar 

  23. Sajan A, Bagla S, Isaacson A (2020) Non-neoplastic disease outside the spine-genicular artery embolization and adhesive capsulitis embolization. Tech Vasc Interv Radiol 23:100702

    Article  Google Scholar 

  24. Crowell-Davis SL (2007) Behavior problems in pet rabbits. J Exotic Pet Med 16:38–44

    Article  Google Scholar 

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Funding

This study has received funding from the National Research Foundation of Korea (Grant No. NRF-2018R1D1A1A02086183) and the Seoul National University Research Fund (Grant No. 0420180840).

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

    Du Hyun Ro & Hyuk-Soo Han

  2. Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Korea

    Myoung-jin Jang

  3. Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

    Jaemoon Koh

  4. Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea

    Won Seok Choi

  5. Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, #101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea

    Hyo-Cheol Kim & Jin Woo Choi

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  1. Du Hyun Ro
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  2. Myoung-jin Jang
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  3. Jaemoon Koh
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  4. Won Seok Choi
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  7. Jin Woo Choi
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Corresponding author

Correspondence to Jin Woo Choi.

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The scientific guarantor of this publication is Jin Woo Choi.

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

Myoung-jin Jang (biostatistician) from the Medical Research Collaborating Centre of Seoul National University Hospital kindly provided statistical advice for this manuscript.

Informed consent

Approval from the institutional animal care committee was obtained.

Ethical approval

Institutional Review Board approval was not required because this is an animal study.

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Ro, D.H., Jang, Mj., Koh, J. et al. Mechanism of action of genicular artery embolization in a rabbit model of knee osteoarthritis. Eur Radiol 33, 125–134 (2023). https://doi.org/10.1007/s00330-022-09006-9

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  • DOI: https://doi.org/10.1007/s00330-022-09006-9

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