The commercial pig as a model of spontaneously-occurring osteoarthritis

Macfadyen, Mhairi A.; Daniel, Zoe; Kelly, Sara; Parr, Tim; Brameld, John M.; Murton, Andrew J.; Jones, Simon W.

Abstract

Background: Preclinical osteoarthritis models where damage occurs spontaneously may better reflect the initiation and development of human osteoarthritis. The aim was to assess the commercial pig as a model of spontaneous osteoarthritis development by examining pain-associated behaviour, joint cartilage integrity, as well as the use of porcine cartilage explants and isolated chondrocytes and osteoblasts for ex vivo and in vitro studies.

Methods: Female pigs (Large white x Landrace x Duroc) were examined at different ages from 6 weeks to 3–4 years old. Lameness was assessed as a marker of pain-associated behaviour. Femorotibial joint cartilage integrity was determined by chondropathy scoring and histological staining of proteoglycan. IL-6 production and proteoglycan degradation was assessed in cartilage explants and primary porcine chondrocytes by ELISA and DMMB assay. Primary porcine osteoblasts from damaged and non-damaged joints, as determined by chondropathy scoring, were assessed for mineralisation, proliferative and mitochondrial function as a marker of metabolic capacity.

Results: Pigs aged 80 weeks and older exhibited lameness. Osteoarthritic lesions in femoral condyle and tibial plateau cartilage were apparent from 40 weeks and increased in severity with age up to 3–4 years old. Cartilage from damaged joints exhibited proteoglycan loss, which positively correlated with chondropathy score. Stimulation of porcine cartilage explants and primary chondrocytes with either IL-1β or visfatin induced IL-6 production and proteoglycan degradation. Primary porcine osteoblasts from damaged joints exhibited reduced proliferative, mineralisation, and metabolic capacity.

Conclusion: In conclusion, the commercial pig represents an alternative model of spontaneous osteoarthritis and an excellent source of tissue for in vitro and ex vivo studies.

Citation

Macfadyen, M. A., Daniel, Z., Kelly, S., Parr, T., Brameld, J. M., Murton, A. J., & Jones, S. W. (2019). The commercial pig as a model of spontaneously-occurring osteoarthritis. BMC Musculoskeletal Disorders, 20, Article 70. https://doi.org/10.1186/s12891-019-2452-0

• Journal Article Type: Article
• Acceptance Date: Feb 1, 2019
• Online Publication Date: Feb 11, 2019
• Publication Date: Feb 11, 2019
• Deposit Date: Mar 13, 2019
• Publicly Available Date: Mar 13, 2019
• Journal: BMC Musculoskeletal Disorders
• Electronic ISSN: 1471-2474
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 20
• Article Number: 70
• DOI: https://doi.org/10.1186/s12891-019-2452-0
• Keywords: Osteoarthritis; Osteoblast; Chondropathy; Pig; Chondrocyte
• Public URL: https://nottingham-repository.worktribe.com/output/1578791
• Publisher URL: https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-019-2452-0
• Additional Information: Received: 14 June 2018; Accepted: 1 February 2019; First Online: 11 February 2019; : This study was approved by the University of Nottingham Animal Welfare Ethical Review Body (AWERB). The collection and use of human OA joint tissue was approved by the National Research Ethics Committee (NRES 13/NE/0222) and written informed consent was obtained from patients.; : Not applicable.; : Dr. Simon Jones is a member of the Editorial Board of BMC Musculoskeletal Disorders. The authors declare that they have no other competing interests.; : Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
• Contract Date: Mar 13, 2019