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Alterations in Hoffa’s fat pad induced by an inflammatory response following idealized anterior cruciate ligament surgery

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Abstract

Objective

To determine whether inflammation following anterior cruciate ligament (ACL) reconstruction leads to long-term pathological changes in the infrapatellar fat pad (IPFP or Hoffa’s fat pad) which could compromise the integrity of the knee joint.

Materials and methods

Sixteen mature sheep underwent anatomic idealized ACL reconstruction surgery (ACL-R) and were sacrificed at 2 weeks (n = 9) and 20 weeks (n = 7) post-ACL-R. Five additional animals served as unoperated controls. A histological grading protocol was developed to quantify the changes in the IPFP post-injury. mRNA expression levels for key markers of inflammation, angiogenesis and tissue regeneration were assessed by qPCR.

Results

The IPFP exhibited altered cellularity and fibrosis at 2 and 20 weeks post-ACL-R. Immunohistochemistry detected macrophage-like cells in the IPFP which were increased at 20 weeks. Specific pro-inflammatory cytokines and IPFP specific adipokines exhibited changes indicating early inflammation mediated alterations. Elevations in CD105 mRNA levels at 2 weeks corroborated the increases in neovascularization observed in the IPFP following injury.

Conclusions

Sustained long-term pathological changes stemming from inflammation are present in IPFP tissue after ACL-R surgery and may compromise the long-term integrity of the knee joint.

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Acknowledgments

The authors gratefully acknowledge the financial support provided for these studies through research grants from the Canadian Institutes for Health Research (MOP-9858 & IMH-120277) (CBF and NGS),The Arthritis Society (SOG-12-04), and an Alberta Innovates Health Solutions Team Grant in Osteoarthritis ((1) 20080170 (2) 200700596) (CBF, NGS and DAH) and Bridge Funding from the Cumming School of Medicine (DAH & NGS). NMS was supported through a studentship from the Alberta Innovates Health Solutions Team Grant in Osteoarthritis. BJH was supported through fellowships from The Arthritis Society and a University of Calgary Queen Elizabeth II Scholarship. NGS is a Killam Memorial Professor and CBF was a McCaig Professor at the McCaig Institute for Bone and Joint Health. The authors thank Leslie Jacques for excellent technical expertise.

Funding

The funds for these studies were obtained from public granting agencies such as Canadian Institutes for Health Research, The Arthritis Society, and an Alberta Innovates Health Solutions Team Grant in Osteoarthritis and Bridge Funding from Cumming School of Medicine. The authors state that there were no private sponsors for this study.

Conflict of interest

The authors declare that there are no competing interests.

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Authors and Affiliations

  1. Cummings School of Medicine, McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB, Canada

    Nathan M. Solbak, Bryan J. Heard, Yamini Achari, May Chung, Nigel G. Shrive, Cyril B. Frank & David A. Hart

  2. Schulich School of Engineering, University of Calgary, Calgary, AB, Canada

    Nigel G. Shrive

  3. Wound Healing Initiative, Biomedical Engineering Program, Department of Surgery, Cummings School of Medicine, McCaig Institute for Bone & Joint Health, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada

    David A. Hart

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  1. Nathan M. Solbak
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  4. May Chung
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  5. Nigel G. Shrive
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  7. David A. Hart
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Corresponding author

Correspondence to David A. Hart.

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Responsible Editor: Jason J. McDougall.

Cyril B. Frank—Deceased.

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Solbak, N.M., Heard, B.J., Achari, Y. et al. Alterations in Hoffa’s fat pad induced by an inflammatory response following idealized anterior cruciate ligament surgery. Inflamm. Res. 64, 615–626 (2015). https://doi.org/10.1007/s00011-015-0840-y

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  • DOI: https://doi.org/10.1007/s00011-015-0840-y

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