Infrapatellar fat pad abnormalities are associated with a higher inflammatory synovial fluid cytokine profile in young adults following ACL tear

Abstract

Objective: To evaluate the degree of knee fat pad abnormalities after acute anterior cruciate ligament (ACL) tear via magnetic resonance fat pad scoring and to assess cross-sectionally its association with synovial fluid biomarkers and with early cartilage damage as quantified via T1r and T2 relaxation time measurements. Design: 26 patients with acute ACL tears underwent 3T MR scanning of the injured knee prior to ACL reconstruction. The presence and degree of abnormalities of the infrapatellar (IPFP) and the suprapatellar (SPFP) fat pads were scored on MR images along with grading of effusion-synovitis and synovial proliferations. Knee cartilage composition was assessed by 3T MR T1r and T2 mapping in six knee compartments. We quantified concentrations of 20 biomarkers in synovial fluid aspirated at the time of ACL reconstruction. Spearman rank partial correlations with adjustments for age and gender were employed to evaluate correlations of MR, particularly cartilage composition and fat pad abnormalities, and biomarker data. Results: The degree of IPFP abnormality correlated positively with the synovial levels of the inflammatory cytokine markers IFN-g (r partial ¼ 0.64, 95% CI (0.26e0.85)), IL-10 (r partial ¼ 0.47, 95% CI (0.04e0.75)), IL-6 (r partial ¼ 0.56, 95% CI (0.16e0.81)), IL-8 (r partial ¼ 0.49, 95% CI (0.06e0.76)), TNF-a (r partial ¼ 0.55, 95% CI (0.14e0.80)) and of the chondrodestructive markers MMP-1 and-3 (MMP-1: r partial ¼ 0.57, 95% CI (0.17 e0.81); MMP-3: r partial ¼ 0.60, 95% CI (0.21e0.83)). IPFP abnormalities were significantly associated with higher T1r and T2 values in the trochlear cartilage (T1r: r partial ¼ 0.55, 95% CI (0.15e0.80); T2: r partial ¼ 0.58, 95% CI (0.18e0.81)) and with higher T2 values in the medial femoral, medial tibial as well as in patellar cartilage (0.45 r partial 0.59). Correlations between SPFP abnormalities and synovial markers were not significant except for IL-6 (r partial ¼ 0.57, 95% CI (0.17e0.81)). Conclusions: This exploratory study suggests that acute ACL rupture can be associated with damage to knee tissues such as the inferior fat pad of the knee. Such fat pad injury could be partially responsible for the apparent post-injury pro-inflammatory response noted in ACL-injured individuals. However, future longitudinal studies are needed to link ACL-rupture associated fat pad injury with important patient outcomes such as the development of posttraumatic osteoarthritis.

Obese and overweight individuals have greater knee synovial inflammation and associated structural and cartilage compositional degeneration: data from the osteoarthritis initiative

“…Synovitis can also be assessed indirectly on NCE-MRI by using the synovial proliferation score. Our group reported the synovial proliferation score as a synovial inflammation marker in young healthy patients with acute ACL rupture and results showed no significant association with average T 2 value and synovial fluid biomarkers obtained at the time of surgery [15]. However, this study showed that synovial proliferation scores at the knee were positively correlated with T 2 values, meniscus and cartilage maximum WORMS grades.…”

“…Interestingly, synovial proliferation in popliteal cysts also showed significant and positive correlations with T 2 values and meniscus lesions by WORMS. One potential explanation for the synovial fluid biomarker findings in the previous ACL tear study [15] could be that synovial proliferation scores measure a chronic change that needs a longer time to develop, so synovial proliferation on MRI would be well demonstrated in a chronic process such as OA rather than in an acute trauma setting. It should also be noted that a previous study showed that synovial thickening detected on NCE-MRI of the knee corresponded to mild chronic synovitis on histo-pathology [52].…”

“…Specifically, six sub-features were graded per knee as described in previous publications (Table 1) [15][16][17][18]. As it is not always possible to differentiate synovial thickening from intra-articular joint fluid on NCE-MRI, we used the term effusion-synovitis as previously described [16,18].…”

“…Grade of signal intensity (SI) was characterized as follows: grade 0 = none; grade 1 = mild (lower than cartilage); grade 2 = moderate (equal to or higher than cartilage but lower than fluid); and grade 3 = severe (equal to fluid). Fifth, the presence and severity of synovial proliferations in the knee were assessed on fat-saturated DESS and IW images, if the effusion-synovitis score was ≥ 1 by either ACLOAS or MOAKS method, in the suprapatellar recess and other visible areas of the joint [15]. Grade 1 corresponded to a smooth synovium, with no proliferation or synovial bands visible; grade 2 was defined as a mild irregularity of the synovium, either focal or diffuse, and the presence of some synovial bands or small bodies; and grade 3 was defined as extensive synovial thickening with irregular villonodular proliferation.…”

Infrapatellar Fat Pad Gene Expression and Protein Production in Patients with and without Osteoarthritis

“…Since these Authors did not analyze IFP and synovial membrane inflammatory cytokines expression, it is not possible to discern the contribution of each joint tissue in the secretion of these inflammatory markers [40].…”