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

• Published in: American journal of translational research 2023-01, Vol.15 (7), p.4573-4586
• Main Authors: Sun, Changqi, Chang, Kenny, Fleming, Braden C, Owens, Brett D, Beveridge, Jillian E, Gage, Andrew, Talley-Bruns, Rachel C, McAllister, Scott, Costa, Meggin Q, Pinette, Megan P, Hague, Madalyn, Molino, Janine, Xiao, Ying, Lu, Shaolei, Wei, Lei
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 1943-8141; 1943-8141

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. 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. The mIAD surgical knees demonstrated greater gross and histological cartilage damage than contralateral (P