New surgical model of post‐traumatic osteoarthritis: Isolated intra‐articular bone injury in the rabbit

Abstract

Osteoarthritis (OA) is a leading cause of disability worldwide. We hypothesized that inflammation following isolated intraarticular bone injury can stimulate post-traumatic OA and developed a rabbit model to test that concept. Sixty female New Zealand White Rabbits were used. Twenty-six experimental animals had two holes drilled into their right femoral-notch, 18 rabbits had sham surgery, and 16 were un-operated controls. Rabbits were euthanized in subgroups at 72 h, 3, 6, 9, and 52 weeks. Knees were assessed grossly and tissues collected. Cartilage and synovium were analyzed with histology and qPCR and subgroups compared statistically. All surgical joints showed gross and histological (modified Mankin score) cartilage damage after surgery, with experimentals worsening with time (p < 0.05). Cartilage qPCR showed fivefold increases in TGFb (p < 0.05) expression at 72 h and 3 weeks with sixfold increases in MMP13 (p < 0.025) expression at 72 h. By 6 weeks, expression of these markers was similar to baseline levels. Synovial membrane thickening with increased cellularity was seen at both 9 and 52 weeks (p < 0.05). Short-term synovial inflammatory marker (IL-1b, IL-Ra, IL-6, and IL-8) expression was three-to fourfold increase in experimentals at 72 h (p < 0.01) returning to baseline levels by 3 weeks. Intra-articular bone injury creates early joint inflammation with some chronic synovial changes and progressive cartilage damage consistent with OA in adult rabbits. This model provides an exciting new avenue to potentially explore some relevant inflammatory drivers of OA without major mechanical variables. ß

Biodegradation of a magnesium alloy implant in the intercondylar femoral notch showed an appropriate response to the synovial membrane in a rabbit model in vivo

“…A study by Huebner et al reported hyperplasia of the lining cell layer and defects in cartilage 9 and 52 weeks after drilling a hole in the femoral notch without using an implant. 31 Those findings show that the operative trauma alone, without any implantation, leads to hyperplasia of the lining cell layer of the synovial membrane.…”

Development and Retranslational Validation of anIn VitroModel to Characterize Acute Infections in Large Human Joints

“…Longer-lasting inflammation inevitably results in a loss of cartilage integrity involving impaired joint function and ultimate destruction [38, 39]. Proinflammatory macrophage derived IL-1 [40] manifested significantly elevated levels in the synovial fluids of affected patients.…”

Improved rehabilitation and functional outcome with dedicated joint irrigation at the end of ACL reconstruction

“…15 Recent animal studies shows that drilling into inter-condylar notch increases Synovial expression levels of IL-1β, IL-6, and IL-8 as well as IL-1Ra were increased 2-3 which subsides after 3 to 4 weeks. 16 Several studies focused on cell/tissue for source of soluble pro-inflammatory product and enzyme mediator (protein of MMP& ADAMT) that initiate inflammation and progressive cartilage loss. tunnels, shaver and threads.…”