Relationship between radiographic changes and symptoms or physical examination findings in subjects with symptomatic medial knee osteoarthritis: a three-year prospective study

<p>Abstract</p> <p>Background</p> <p>Although osteoarthritis (OA) of the knee joints is the most common and debilitating joint disease in developed countries, the factors that determine the severity of symptoms are not yet understood well. Subjects with symptomatic medial knee OA were followed up prospectively to explore the relationship between radiographic changes and symptoms or physical examination findings.</p> <p>Methods</p> <p>One-hundred six OA knees in 68 subjects (mean age 71.1 years; 85% women) were followed up at 6-month intervals over 36 months. At each visit, knee radiographs were obtained, symptoms were assessed by a validated questionnaire, and the result of physical examination was recorded systematically using a specific chart. Correlations between the change of radiographs and clinical data were investigated in a longitudinal manner.</p> <p>Results</p> <p>During the study period, the narrowing of joint space width (JSW) was observed in 34 joints (32%). Although those knees were clinically or radiographically indistinguishable at baseline from those without JSW narrowing, differences became apparent at later visits during the follow-up. The subjects with knees that underwent JSW narrowing had severer symptoms, and the symptoms tended to be worse for those with higher rates of narrowing. A significant correlation was not found between the severity of symptoms and the growth of osteophytes. For the knees that did not undergo radiographic progression, the range of motion improved during the follow-up period, possibly due to the reduction of knee pain. Such improvement was not observed with the knees that underwent JSW narrowing or osteophyte growth.</p> <p>Conclusion</p> <p>The result of this study indicates that the symptoms of knee OA patients tend to be worse when JSW narrowing is underway. This finding may explain, at least partly, a known dissociation between the radiographic stage of OA and the severity of symptoms.</p

Proinflammatory role of amphiregulin, an epidermal growth factor family member whose expression is augmented in rheumatoid arthritis patients-3

REG and/or genistein. After 4 h of stimulation, total RNAs were extracted and the mRNA levels of PDGF, bFGF, VEGF, IL-1β, IL-6, IL-8, TNF-α and GM-CSF were measured by real-time PCR. The results for VEGF, IL-8, GM-CSF and IL-6 are shown. The results for the other molecules were omitted from the figure, since AREG had no effect on their expressions. (B) Effects of AREG on cytokine production by RA-FLS. Four RA-FLS lines were cultured with the indicated concentrations of AREG for 24 h. The GM-CSF, IL-6, IL-8 and VEGF concentrations in the supernatants were measured by ELISA, and are shown as means ± SD. (C) Effects of AREG on the expression of sheddases. The same cDNA samples used in panel A were subjected to real-time PCR analysis for ADAM10 and ADAM17. The results for ADAM10 were omitted from the figure, since they were similar to those for ADAM17. Each panel shows a representative result of three independent experiments. Significant differences from unstimulated cells are shown by asterisks (*P < 0.05; **P < 0.01).<p><b>Copyright information:</b></p><p>Taken from "Proinflammatory role of amphiregulin, an epidermal growth factor family member whose expression is augmented in rheumatoid arthritis patients"</p><p>http://www.journal-inflammation.com/content/5/1/5</p><p>Journal of Inflammation (London, England) 2008;5():5-5.</p><p>Published online 27 Apr 2008</p><p>PMCID:PMC2396620.</p><p></p

Proinflammatory role of amphiregulin, an epidermal growth factor family member whose expression is augmented in rheumatoid arthritis patients-4

S (left). Significant differences from unstimulated cells are shown by asterisks (*P < 0.05). The correlation between the mRNA levels of VEGF and AREG is shown by a distribution chart (right). The linear regression coefficient (R) is 0.496 and the correlation coefficient (ρ) is 0.700 (P = 0.0067). (B) The concentrations of VEGF in synovial fluids from 7 RA patients and 6 OA patients were measured by ELISA, and are shown by box-plots (left). Significant differences from unstimulated cells are shown by asterisks (*P < 0.05). The correlation between the protein concentrations of VEGF and AREG is shown by a distribution chart (right), in which Ris 0.577 and ρ is 0.772 (P = 0.0075).<p><b>Copyright information:</b></p><p>Taken from "Proinflammatory role of amphiregulin, an epidermal growth factor family member whose expression is augmented in rheumatoid arthritis patients"</p><p>http://www.journal-inflammation.com/content/5/1/5</p><p>Journal of Inflammation (London, England) 2008;5():5-5.</p><p>Published online 27 Apr 2008</p><p>PMCID:PMC2396620.</p><p></p

Proinflammatory role of amphiregulin, an epidermal growth factor family member whose expression is augmented in rheumatoid arthritis patients-1

Ces are shown by asterisks (**P < 0.01). RA: samples from RA patients; OA: samples from OA patients; HC: samples from healthy volunteers. (B) The AREG mRNA expression levels in PBMCs and AREG protein concentrations in plasma are shown. Venous blood samples from 6 RA patients and 6 healthy volunteers (HC) were separated into plasma and PBMCs. Total RNAs were extracted from PBMCs and subjected to cDNA synthesis. The AREG mRNA levels were measured by real-time PCR and normalized by the GAPDH mRNA levels. The relative AREG mRNA level relative to the GAPDH mRNA level is plotted as the log ratio on the primary y-axis (left), while the plasma concentration of AREG protein measured by ELISA is plotted as the log value on the secondary y-axis (right). The correlation coefficient (ρ) of the protein level in plasma to the mRNA level in PBMCs is -0.378 (P = 0.2104). (C) PBMCs from 4 RA patients and 2 HCs were separated by CD14 microbeads, and the AREG mRNA level in each fraction was measured by real-time PCR. The log ratio of the AREG mRNA level relative to the GAPDH mRNA level is plotted on the y-axis.<p><b>Copyright information:</b></p><p>Taken from "Proinflammatory role of amphiregulin, an epidermal growth factor family member whose expression is augmented in rheumatoid arthritis patients"</p><p>http://www.journal-inflammation.com/content/5/1/5</p><p>Journal of Inflammation (London, England) 2008;5():5-5.</p><p>Published online 27 Apr 2008</p><p>PMCID:PMC2396620.</p><p></p

Proinflammatory role of amphiregulin, an epidermal growth factor family member whose expression is augmented in rheumatoid arthritis patients-5

B, C) is plotted on the y-axis of each graph. The upper and lower error bars indicate the 90th and 10th percentiles, respectively. The upper and lower edges of each box indicate the 75th and 25th percentiles, respectively, and the line inside the box shows the median. Genes not detected are shown as ND. The differences between the mRNA levels in the RA and control samples were analyzed by the Mann-Whitney U-test, and significant differences are shown by asterisks (*P < 0.05; **P < 0.01). RA: samples from RA patients; OA: samples from OA patients.<p><b>Copyright information:</b></p><p>Taken from "Proinflammatory role of amphiregulin, an epidermal growth factor family member whose expression is augmented in rheumatoid arthritis patients"</p><p>http://www.journal-inflammation.com/content/5/1/5</p><p>Journal of Inflammation (London, England) 2008;5():5-5.</p><p>Published online 27 Apr 2008</p><p>PMCID:PMC2396620.</p><p></p

Proinflammatory role of amphiregulin, an epidermal growth factor family member whose expression is augmented in rheumatoid arthritis patients-2

REG. After 24 h of stimulation, the cells were labeled with H-thymidine for 18 h and then harvested on glass filters with a cell harvester. The incorporated radioactivity was measured by liquid scintillation counting. The values are shown as the means ± SD of three independent experiments. Significant differences are shown by asterisks (*P < 0.05; **P < 0.01). (B) Expression profiles of EGFR family members in FLS. cDNA samples of the four FLS lines used in the proliferation assay were subjected to real-time PCR analysis. (C) Expression profiles of the receptors and sheddases of the EGF family in synovia. cDNAs of synovial tissues from 10 RA patients and 6 OA patients were subjected to real-time PCR analysis.<p><b>Copyright information:</b></p><p>Taken from "Proinflammatory role of amphiregulin, an epidermal growth factor family member whose expression is augmented in rheumatoid arthritis patients"</p><p>http://www.journal-inflammation.com/content/5/1/5</p><p>Journal of Inflammation (London, England) 2008;5():5-5.</p><p>Published online 27 Apr 2008</p><p>PMCID:PMC2396620.</p><p></p