Extracellular matrix changes in response to recombinant human fibroblast growth factor 18 studied in ex vivo cultures of articular cartilage

Abstract

s / Osteoarthritis and Cartilage 22 (2014) S57–S489 S77 posterior view radiograph of painful knee were measured at baseline and 3 years later. Experienced readers read the radiographs independently recorded the radiographic features of Kellgren & Lawrence grading (K/L) grade and joint spacewidth (JSW). JSWwas determined at the center point of the medial femoro-tibial compartment on a radiograph using a 0.1-mm graduated magnifying lens.Both serum and urine samples were obtained on the day that baseline radiographs taken. Measurement of uCTX-II was used commercial enzyme-linked immunesorbent assay kit (CartiLaps; Nordic Bioscience, Herlev, Denmark). uCTX-II values were corrected for urine creatinine concentration. As the distribution of uCTX-II was found to be positively skewed, a logarithmic transformation (natural log (Ln)) was therefore applied to these biomarkers to obtain an approximately normal distribution. uCTX-II were compared using parametric comparisons analysis of variance (ANOVA). The Bonferroni correction for multiple comparisons was applied. Significant differences were evaluated t-test if ANOVAwas significant. A Pvalue of less than or equal to 0.05 was considered to be statistically significant. Results: Of the 91patients, 7 showed K/L grade 1,16 showed K/L grade 2, 27 showed K/L grade 3 and 41 showed K/L grade 4 at the baseline. In the 3 years, 41 patients were received total knee arthroplasty (TKA). In the other patients, 22 patients were progressed their K/L grade one ormore. The ln-uCTX at baseline was not significant differences between K/L grades. Among the patients with K/L grade 1 to 3, the baseline ln-uCTXII levels in the patients with progression of K/L grade were significantly higher than the patients with no progression of K/L grade (p 1⁄4 0.002). Conclusions: We demonstrated in the present study that the patients who were progressed OA presented by K/L grade during 3 years had a higher uCTX-II, cartilage degradation marker, levels than the others. These findings suggest that we could predict OA progression at the first visit in the hospital be using biomarkers. In conclusion, uCTX-II could predict OA progression. 122 COLL2-1NO2: A BIOMARKER FOR EARLY KNEE OSTEOARTHRITIS? M.L. Landsmeer y, J. Runhaar y, Y.E. Henrotin z, M. van Middelkoop y, E.H. Oei x, D. Vroegindeweij k, P. van der Plas k, M. Reijman{, G. van Osch{, P. Bindels y, S.M. Bierma-Zeinstra#. yDept. of Gen. Practice, Erasmus MC, Univ. Med. Ctr., Rotterdam, Netherlands; zBone and Cartilage Res. Unit, Univ. of Li ege, Li ege, Belgium; xDept. of Radiology, Erasmus MC, Univ. Med. Ctr., Rotterdam, Netherlands; kDept. of Radiology, Maasstad Hosp., Rotterdam, Netherlands; {Dept. of Orthopaedics, Erasmus MC, Univ. Med. Ctr., Rotterdam, Netherlands; Dept. of Gen. Practice, Dept. of Orthopaedics, Erasmus MC, Univ. Med. Ctr., Rotterdam, Netherlands Purpose: To investigate the association between urinary degradation biomarker Coll2-1NO2 (uColl2-1NO2) and incident knee OA after 2.5 years in middle-aged overweight women at high risk for knee OA. Secondly, to assess association of uColl2-1NO2 with cartilage loss progression on magnetic resonance imaging (MRI). Methods: Data were used from PROOF, a 2.5 years randomized controlled trial evaluating the preventive effects of a diet and exercise program and of oral glucosamine sulphate (double blind and placebo controlled), on development of knee OA in women with body mass index 27 kg/m2 and without knee OA at baseline. Baseline, 1 and 2.5 years uColl2-1NO2 levels were assessed with ELISA. Primary outcome measure was incidence of knee OA in one or both knees, defined as incidence of either Kellgren & Lawrence grade 2, joint space narrowing of 1.0 mm or clinical knee OA according to the combined clinical and radiographic ACR-criteria. Secondary outcome measures were the separate radiographic and clinical items and the MRI progression of cartilage loss in the patellofemoral and tibiofemoral joint, using the MRI Osteoarthritis Knee Score (MOAKS). Association between baseline, follow-up and change of uColl2-1NO2 with primary and secondary outcomes were assessed using binary logistic regression analyses. Results: 254 women were available for primary analysis, 234 women for MRI analyses. After 2.5 years follow-up, knee OA developed in 72 of 254 women (28.3%) and progression of cartilage defects in 115 of 234 women (49.1%). An inversed association was found between baseline uColl2-1NO2 and incident knee OA (OR 0.74, 95% CI 0.55 – 0.99) after 2.5 years follow-up. A trend of increasing uColl2-1NO2 during follow-up of 2.5 years was found in incident knee OA and in progression of cartilage defects (OR 1.10, 95% CI 0.81 – 1.48 and OR 1.26, 95% CI 0.93 – 1.70 respectively). This trend of increasing uColl2-1NO2 is also shown in the figure. Conclusion: In overweight middle-aged women, low baseline uColl21NO2 levels were associated with an increased risk for incident knee OA. We can propose different hypothesis to explain this finding: 1) an anabolic compensatory mechanism active in early knee OA, 2) in contrast, a decrease of cartilage metabolism could precede cartilage degradation; 3) cartilage volume is lower in people developing knee OA. Overall, after lower baseline uColl2-1NO2, increasing uColl2-1NO:2 levels seem to dominate in further OA development. Although in early knee OA changes in uColl2-1NO2 can be found, further exploring of the biomarker field seems necessary to better understand the onset of OA in high risk patients. 123 CORRELATION ANALYSIS OF INFLAMMATION BIOMARKERS WITH CLINICAL SCORES OF TISSUEGENE-C (TG-C) B. Lee, J. Cho, T. Kim, Y. Park, Y. Kwon, M. Noh, K-H. Lee. Kolon Life Sci., Inc., Gwacheon-si, Republic of Korea Purpose: Osteoarthritis (OA) is a degenerative joint disease caused by unbalanced anabolism and catabolism of cartilage with a mild inflammatory response, but little is known about how the level of inflammation is related to severity of OA symptom and tissue destruction. The level of circulating acute phase protein, C-reactive protein (CRP) has been widely used as a diagnostic marker in acute inflammatory diseases. The matrix metalloproteinase-mediated C-reactive protein (CRPM) is a hallmark of chronic tissue inflammation in the knee joint of OA patients. TG-C is a cell mediated gene therapy product that contains non-transduced (hChonJ) and transduced (hChonJb#7) human allogeneic chondrocytes. The hChonJb#7 cells were transduced with TGF-b1 gene-containing retroviral vector. The aim of this study was to evaluate correlation between inflammatory biomarkers in OA patients and the changes of clinical scores of IKDC and WOMAC to estimate the prognostic feature for this TG-C therapy. Methods: Data from clinical scores of IKDC, WOMAC, IKDC6-0(the changed value of IKDC score evaluated 6months post treatment of TGC) and WOMAC6-0(the changed value of WOMAC score evaluated 6 months post treatment of TG-C) were collected from patients during TG-C clinical trials, phase IIa (KS-TGC-01-2a) and phase IIb (KS-TGC-012b). The patients enrolled in the clinical trials of TG-C included advanced joint damage (K&L grade 3, ICRS grade IV in main cartilage lesion) and various range of knee clinical scores (Table 1). The level of serum high sensitive CRP (hsCRP) and CRPM were detected by enzyme linked immunosorbent assay (ELISA). The values were compared between studies and treatment groups within each study by a non-