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

Abstract

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

Citation

Staines, K., Ikpegbu, E., Törnqvist, A., Dillon, S., Javaheri, B., Amin, A. K., Clements, D. N., Buttle, D. J., Pitsillides, A. A., & Farquharson, C. (2019). Conditional deletion of E11/podoplanin in bone protects against load-induced osteoarthritis. BMC Musculoskeletal Disorders, 20, Article 344 (2019). https://doi.org/10.1186/s12891-019-2731-9

• 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)
• DOI: https://doi.org/10.1186/s12891-019-2731-9
• Keywords: osteocytes, subchondral bone, osteoarthritis, E11/podoplanin
• Public URL: http://researchrepository.napier.ac.uk/Output/1980008
• Contract Date: Jul 22, 2019