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

Staines, Katherine; Ikpegbu, Ekele; Törnqvist, Anna; Dillon, Scott; Javaheri, Behzad; Amin, Anish K.; Clements, Dylan N.; Buttle, David J.; Pitsillides, Andrew A.; Farquharson, Colin


Katherine Staines

Ekele Ikpegbu

Anna Törnqvist

Scott Dillon

Behzad Javaheri

Anish K. Amin

Dylan N. Clements

David J. Buttle

Andrew A. Pitsillides

Colin Farquharson


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


Staines, K., Ikpegbu, E., Törnqvist, A., Dillon, S., Javaheri, B., Amin, A. K., …Farquharson, C. (2019). Conditional deletion of E11/podoplanin in bone protects against load-induced osteoarthritis. BMC Musculoskeletal Disorders, 20, Article 344 (2019).

Journal Article Type Article
Acceptance Date Jul 19, 2019
Online Publication Date Jul 27, 2019
Publication Date Jul 27, 2019
Deposit Date Jul 22, 2019
Publicly Available Date Jul 22, 2019
Electronic ISSN 1471-2474
Publisher BMC
Peer Reviewed Peer Reviewed
Volume 20
Article Number 344 (2019)
Keywords osteocytes, subchondral bone, osteoarthritis, E11/podoplanin
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Copyright Statement
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (

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