Lower TRAcP 5B ups phosphorylated osteopontin in rheumatoid arthritis
Reduced levels of tartrate-resistant acid phosphatase (TRAcP) 5B isoform in synovial fluid of rheumatoid arthritis (RA) patients lead to higher concentrations of proinflammatory phosphorylated osteopontin (phospho-OPN), a new study has shown.
Using western blot analysis, concentrations of phospho-OPN were measured from synovial fluid samples collected from 24 osteoarthritis (OA; mean age 70.31±8.30 years) and 24 RA patients, 14 of whom were seropositive (mean age 69.21±7.93 years) and 10 were seronegative (mean age 70.90±6.33).
TRAcP levels were measured using enzyme-linked immunosorbent assay. The Mann-Whitney test for continuous variables was used to evaluate statistical significance.
Mean phospho-OPN levels, measured by relative optical density (ROD), in both seropositive (0.200±0.018 ROD) and seronegative (0.192±0.027 ROD) RA patients were significantly higher than in OA patients (0.153±0.017 ROD; p<0.05 for both). There were no significant difference between the seropositive and seronegative RA patients, and in levels of full-length OPN.
Twelve synovial fluid samples had undetectable levels of both TRAcP 5A and 5B isoforms. In the remaining samples, TRAcP 5A was notably higher in seropositive RA patients while 5B was higher in OA patients. There were no significant differences among the groups, however.
The ratio of TRAcP 5B/5A was marginally lower in seropositive RA patients (mean ratio, 0.714±0.259) than in OA (mean ratio, 1.384±0.275) and seronegative RA (mean ratio, 1.388±0.680) patients (p=0.07).
TRAcP 5B/5A was significantly negatively correlated to full-length phospho-OPN (p<0.05), indicating that higher levels of the 5B isoform lead to lower OPN phosphorylation.
These findings may explain increased activation of osteoclasts and macrophages, which cause local inflammation and bone resorption in joints with RA.