Contribution of IL-1β, 6 and TNF-α to the form of post-traumatic osteoarthritis induced by "idealized" anterior cruciate ligament reconstruction in a porcine model.
BACKGROUND
It has been noted that anterior cruciate ligament (ACL) injury-induced cartilage degeneration is the key risk factor for post-traumatic osteoarthritis (PTOA). However, whether the cartilage degeneration after ACL injury is caused by inflammation, abnormal biomechanics or both remains largely unknown, as there has been no animal model for separating the two factors so far.


METHODS
Eighteen-month-old female mini-pigs were divided into an "idealized" anterior cruciate ligament reconstruction (IACLR) group and a 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 (including interferon [IFN]-γ, interleukin [IL]-1β, IL-4, IL-6, IL-8, IL-10, IL-12 and tumor necrosis factor [TNF]-α measured by the Luminex method) and changes in cartilage histology (quantified by morphological scoring) after surgery.


RESULTS
A significant OA cartilage damage with increased MMP-1, MMP-13 mRNA levels and reduced aggrecan mRNA/protein levels was observed in IACLR groups. As a result, the IACLR gross morphology score was dramatically increased than control. Moreover, IACLR significantly increased the levels of IL-1β, IL-4, IL-6 and TNF-α in the synovial fluid of the knee. Most importantly, a close relationship was found between IL-1β, IL-6 and TNF-α concentrations and morphological score of PTOA, respectively.


CONCLUSION
These results demonstrated that inflammatory factors are independently responsible for the onset of PTOA.
['Han|Peng-Fei|PF|', 'Wei|Lei|L|', 'Duan|Zhi-Qing|ZQ|', 'Zhang|Zhi-Liang|ZL|', 'Chen|Tao-Yu|TY|', 'Lu|Jian-Gong|JG|', 'Zhao|Rui-Peng|RP|', 'Cao|Xiao-Ming|XM|', 'Li|Peng-Cui|PC|', 'Lv|Zhi|Z|', 'Wei|Xiao-Chun|XC|']
D000818:Animals D016118:Anterior Cruciate Ligament D000070598:Anterior Cruciate Ligament Injuries D059549:Anterior Cruciate Ligament Reconstruction D004195:Disease Models, Animal D005260:Female D006801:Humans D018836:Inflammation Mediators D053583:Interleukin-1beta D015850:Interleukin-6 D020370:Osteoarthritis, Knee D011183:Postoperative Complications D013552:Swine D013556:Swine, Miniature D014409:Tumor Necrosis Factor-alpha
Post-traumatic osteoarthritis Anterior cruciate ligament reconstruction Mini-pig Knee