The mechanisms of PTOA following anterior cruciate ligament (ACL) injury are likely due to the biological and mechanical insults at the time of injury. These patients still remain at high risk for PTOA after treated with ACL reconstruction (ACL-R). We do not know if the cartilage degeneration after ACL-R is primarily due to abnormal mechanics, inflammation or both. “Idealized” ACLR model (restore normal joint kinematic) was used to test if inflammatory factors are responsible for PTOA.
Eighteen-month-old female mini-pigs were divided into “idealized” anterior cruciate ligament reconstruction (IACLR) group and control group (n=16 limbs per group). Real-time PCR, safranine O staining and indian ink staining were performed to verify whether animal models were successfully established or not. Multiple linear regression analysis was used to evaluate the correlation between levels of the inflammatory factors by the Luminex (including interferon [IFN]-γ, interleukin [IL]-1β, IL-4, IL-6, IL-8, IL-10, IL-12 and tumor necrosis factor [TNF]-α) and changes in cartilage histology (quantified by morphological scoring) after surgery.
A significant OA cartilage damage with increased MMP-1, MMP-13 mRNA levels and reduced the level of aggrecan mRNA/protein was observed in IACLR groups. Gross morphology score from IACLR animals was dramatically increased compared with control. Moreover, IACLR animals significantly increased the levels of IL-1β, IL-4, IL-6 and TNF-α in the synovial fluid of the knee compared with control. The levels of IL-1β, IL-6 and TNF-α are correlated with morphological score of PTOA.
IACLR is well-known restoring normal joint kinematic model. These results demonstrated that inflammatory factors are independently responsible for the onset of PTOA.