Early joint tissue changes are highly correlated with a set of inflammatory and degradative synovial biomarkers after ACL autograft and its sham surgery in an ovine model

Abstract

While impossible in humans, the mechanisms of early cartilage, bone and meniscal damage can be quantified after anterior cruciate ligament (ACL) injury in animal models. We utilized an ovine model to determine if the mRNA expression of inflammatory and degradative molecules (IL-1b, IL-6, MMP-1, 2, 3, and 13) in the synovium correlated to changes in joint tissues 2 weeks post-ACL surgery, to test the hypothesis that synovial inflammation is a marker of these changes and possibly their originator. Nine ''idealized'' ACL autografts were performed and compared with three sham and six normal animals. Using validated protocols, early osteophyte formation, articular cartilage, and meniscal damage were quantified. Synovium was harvested and mRNA expression quantified using qPCR. Multiple linear regression analysis (MLRA) was utilized to correlate synovial mRNA expression in treated and contra-lateral limbs, from all treatment groups with corresponding joint scores. Synovial mRNA expression was significantly elevated in all experimental and sham joints. The MLRA model was a significant predictive tool (p ¼ 0.001, R 2 ¼ 0.70) of gross tissue scores with significant contributions from IL-1b, IL-6, and MMP-3. Findings suggest that this set of synovial biomarkers is predictive (p < 0.009) of early gross changes of joint tissues after arthrotomy and likely directly involved in the relevant mechanisms, particularly early osteophyte formation, in vivo. ß

Carrageenan-induced transient inflammation in a rabbit knee model: molecular changes consistent with an early osteoarthritis phenotype

“…Interestingly, in the present study we observed that both the synovium and the cartilage tissue from the femoral condyle and the tibial plateau region exhibited concurrent expression of inflammatory markers. Such results clearly show that injection of carrageenan in the joint environment has an influence on both the cartilage and the synovium, similar to the previous reports on ACL autograft model studies [36].…”

“…The results presented in this report indicate that a single injection of carrageenan into the rabbit knee leads to the elevated expression of MMPs and cytokines, not unlike that previously observed following an ACL injury and early OA development [34][35][36]. In the present study, the inflammatory response in synovial tissue peaked at 2 weeks post-carrageenan treatment, as exhibited by significant elevation in mRNA levels for IL-1b and IL-6.…”

Brucella abortus Invasion of Synoviocytes Inhibits Apoptosis and Induces Bone Resorption through RANKL Expression

“…abortus infection inhibits apoptosis induced by supernatants from B. abortus-infected monocytes and neutrophils. Neutrophils and monocytes have been shown to induce apoptosis of cells from infiltrated tissues due to the release of MMPs, reactive oxygen species, and TNF-␣ (34,44,45). However, our results indicate that B. abortus infection inhibits apoptosis of synoviocytes induced by STS.…”

Potential of Tissue-Engineered Ligament Substitutes for Ruptured ACL Replacement

“…However, other possibilities likely also exist. In studies of partial injuries to the ACL in either rabbit (Lo et al, in preparation; Heubner et al, in preparation) or sheep models (Heard et al, 2011), the response to injury leads to an inflammation. In fact, a partial injury to one band of the ACL leads to an initial response not dissimilar to that of the MCL at 3 weeks post-injury, which then fails to mature and ultimately fails to lead to functional repair, possibly due to persistent inflammation (Lo et al, in preparation).…”