Prokineticin 2 and Cytokine Content in the Synovial Fluid of Knee Osteoarthritis and Traumatic Meniscal Tear Patients: Preliminary Results

Abstract

Knee osteoarthritis (OA) is a chronic degenerative inflammatory-based condition caused by a cascade of different intra-articular molecules including several cytokines. Among the cytokines, prokineticins (PKs) have recently been identified as important mediators of inflammation and pain. This observational study examined the potential involvement of PK2 in degenerative or traumatic knee disease. Fifteen patients presenting knee osteoarthritis (OA group) and 15 patients presenting a traumatic meniscal tear (TM group) were studied. Synovial fluid samples from affected knees were assessed for PK2, IL-10, and TNF-α using the ELISA method. At a long-term follow-up (minimum 5 years, mean = 6.1 years), patients in the TM group underwent clinical re-evaluation with PROMs (Tegner Activity Scale, IKDC, Lysholm, SKV); in addition, X-ray visualization was used to assess the presence of secondary OA. PK2 was detected in synovial fluids of both TM and OA patients and the levels were comparable between the two groups, while IL-10 levels were significantly greater in the OA group than those in TM patients. PK2 levels correlated with those of IL-10. PK2 levels were greater in blood effusions compared to clear samples, did not differ significantly between sexes, nor were they related to differences in weight, height, or injury (meniscal laterality, time since dosing). No correlation was found between PROMs and radiological classifications in patients in the TM group at final follow-up. These data are the first observations of PK2 in synovial fluid following traumatic meniscus injury. These findings suggest possible further prognostic indices and therapeutic targets to limit the development of secondary OA.

Keywords: cytokines; knee; meniscus; osteoarthritis; prokineticins; synovial.

Figure 1

PK2 and cytokine content in synovial fluid. PK2 (a), TNF alpha (b), and IL-10 (c) in the synovial fluid of knee osteoarthritis (OA) and Traumatic Meniscal (TM) patients. Solid circles and solid squares represent PK2 and cytokines synovial fluid content of each single patient in OA (circle) and TM (square) group. The levels of biomolecules are expressed as pg/mL. **** p < 0.0001 Mann–Whitney test.

Figure 1

PK2 and cytokine content in synovial fluid. PK2 (a), TNF alpha (b), and IL-10 (c) in the synovial fluid of knee osteoarthritis (OA) and Traumatic Meniscal (TM) patients. Solid circles and solid squares represent PK2 and cytokines synovial fluid content of each single patient in OA (circle) and TM (square) group. The levels of biomolecules are expressed as pg/mL. **** p < 0.0001 Mann–Whitney test.

Figure 2

Effect of elapsed time between traumatic injury and synovial fluid sampling on PK2 levels. PK2 levels (pg/mL) were reported in Sub-acute group (SA, synovial fluid sample collected from 3 to 90 days after injury) and in Chronic group (C, synovial fluid sample collected greater than 90 days after injury) belonging to both TM and OA groups. Solid circles represent PK2 synovial fluid content of each single patient.

Figure 3

Effect of synovial fluid quality on PK2 levels. PK2 levels were evaluated (pg/mL) in hematologic (hemarthrosis) and clear (hydrarthosis) synovial fluid samples of Knee Osteoarthritis patients (OA group). * p < 0.05 Mann–Whitney test. Solid circles represent PK2 synovial fluid content of each single patient.

Figure 4

Correlation between age of patients and PK2 levels. The effect of age on PK2 levels in the synovial fluid was evaluated in Knee Osteoarthritis (OA group; (a)) and in Traumatic Meniscal (TM group; (b) patients and in the pooled OA+TM population (c). Correlations were investigated using the non-parametric Spearman rank correlation coefficient test. R and significant p-value are reported in figure; * p < 0.05. Solid circles represent values of each single patient.

Figure 4

Correlation between age of patients and PK2 levels. The effect of age on PK2 levels in the synovial fluid was evaluated in Knee Osteoarthritis (OA group; (a)) and in Traumatic Meniscal (TM group; (b) patients and in the pooled OA+TM population (c). Correlations were investigated using the non-parametric Spearman rank correlation coefficient test. R and significant p-value are reported in figure; * p < 0.05. Solid circles represent values of each single patient.

Figure 5

Correlation between cytokines and PK2 measured in the synovial fluid. PK2 levels in the synovial fluid were correlated to that of IL-10 and TNFalpha measured in Knee Osteoarthritis (OA group; (a,b)) and in Traumatic Meniscal (TM group; (c,d)) groups. Correlations among molecules were investigated using the non-parametric Spearman rank correlation coefficient test. r and significant p-value are reported in figure; * p < 0.05; ** p < 0.01. Solid circles represent values of each single patient.

Figure 5

Correlation between cytokines and PK2 measured in the synovial fluid. PK2 levels in the synovial fluid were correlated to that of IL-10 and TNFalpha measured in Knee Osteoarthritis (OA group; (a,b)) and in Traumatic Meniscal (TM group; (c,d)) groups. Correlations among molecules were investigated using the non-parametric Spearman rank correlation coefficient test. r and significant p-value are reported in figure; * p < 0.05; ** p < 0.01. Solid circles represent values of each single patient.