Research Output

Conditional deletion of E11/podoplanin in bone protects against load-induced osteoarthritis

  Background: Subchondral bone (SCB) thickening is one of the earliest detectable changes in osteoarthritic joints and is considered a potential trigger for subsequent articular cartilage degeneration. In this manuscript, we examine whether disruption to the SCB osteocyte network contributes to the initiation and pathogenesis of osteoarthritis.

Methods: We examined expression patterns of the glycoprotein E11/podoplanin by immunohistochemical labelling in murine, human and canine osteoarthritis models. We also examined the effects of twice-weekly administration of Bortezomib, a proteasome inhibitor which stabilises osteocyte E11 levels, to C57/BL6 wild-type male mice (1mg/kg/day) for 8 weeks after surgical destabilisation of the medial meniscus. By inducing osteoarthritis-like changes in the right knee joint of 12‐week‐old male E11 hypomorphic mice (and corresponding controls) using a post-traumatic joint loading model, we also investigated whether a bone-specific E11 deletion in mice increases joint vulnerability to osteoarthritis. Articular cartilage degradation and osteophyte formation were assessed by histology and in line with the OARSI grading system.

Results: Our studies reveal increased E11 expression in osteocytes of human and canine osteoarthritic SCB. We found that Bortezomib administration had no effect on surgically-induced osteoarthritis, potentially due to a lack of the expected stabilisation of E11 in the SCB. We also found, in concordance with our previous work, wild-type mice exhibited significant load-induced articular cartilage lesions on the lateral femoral condyle (p

  • Type:

    Article

  • Date:

    27 July 2019

  • Publication Status:

    Published

  • DOI:

    10.1186/s12891-019-2731-9

  • Library of Congress:

    RC Internal medicine

  • Dewey Decimal Classification:

    616.7 Diseases of musculoskeletal system

  • Funders:

    Arthritis Research UK; Tenovus Scotland; Biotechnology and Biological Sciences Research Council

Citation

Staines, K., Ikpegbu, E., Törnqvist, A., Dillon, S., Javaheri, B., Amin, A. K., …Farquharson, C. (in press). Conditional deletion of E11/podoplanin in bone protects against load-induced osteoarthritis. BMC Musculoskeletal Disorders, 20, https://doi.org/10.1186/s12891-019-2731-9

Authors

Keywords

osteocytes, subchondral bone, osteoarthritis, E11/podoplanin

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