A novel large animal model of posttraumatic osteoarthritis induced by inflammation with mechanical stability

Changqi Sun; Kenny Chang; Braden C Fleming; Brett D Owens; Jillian E Beveridge; Andrew Gage; Rachel C Talley-Bruns; Scott McAllister; Meggin Q Costa; Megan P Pinette; Madalyn Hague; Janine Molino; Ying Xiao; Shaolei Lu; Lei Wei

A novel large animal model of posttraumatic osteoarthritis induced by inflammation with mechanical stability

Am J Transl Res. 2023 Jul 15;15(7):4573-4586. eCollection 2023.

Authors

Affiliations

¹ Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital Providence, RI, USA.
² Cleveland Clinic Biomedical Engineering Department Cleveland, OH, USA.

PMID: 37560216
PMCID: PMC10408525

Abstract

Objectives: Animal models are needed to reliably separate the effects of mechanical joint instability and inflammation on posttraumatic osteoarthritis (PTOA) pathogenesis. We hypothesized that our modified intra-articular drilling (mIAD) procedure induces cartilage damage and synovial changes through increased inflammation without causing changes in gait.

Methods: Twenty-four Yucatan minipigs were randomized into the mIAD (n=12) or sham control group (n=12). mIAD animals had two osseous tunnels drilled into each of the tibia and femur adjacent to the anterior cruciate ligament (ACL) attachment sites on the left hind knee. Surgical and contralateral limbs were harvested 15 weeks post-surgery. Cartilage degeneration was evaluated macroscopically and histologically. Synovial changes were evaluated histologically. Interleukin-1 beta (IL-1β), nuclear factor kappa B (NF-κB), and tumor necrosis factor alpha (TNF-α) mRNA expression levels in the synovial membrane were measured using quantitative real-time polymerase chain reaction. IL-1β and NF-κB levels in chondrocytes were assessed using immunohistochemistry. Load asymmetry during gait was recorded by a pressure-sensing walkway system before and after surgery.

Results: The mIAD surgical knees demonstrated greater gross and histological cartilage damage than contralateral (P<.01) and sham knees (P<.05). Synovitis was present only in the mIAD surgical knee. Synovial inflammatory marker (IL-1β, NF-κB, and TNF-α) expression was three times higher in the mIAD surgical knee than the contralateral (P<.05). Chondrocyte IL-1β and NF-κB levels were highest in the mIAD surgical knee. In general, there were no significant changes in gait.

Conclusions: The mIAD model induced PTOA through inflammation without affecting gait mechanics. This large animal model has significant applications for evaluating the role of inflammation in PTOA and for developing therapies aimed at reducing inflammation following joint injury.

Keywords: Posttraumatic osteoarthritis; gait; inflammation; minipig; synovium.

Abstract

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