Objective: To evaluate the correlation between synovial tumor necrosis factor receptor-associated factor (TRAF) 6 expression and serum bone metabolism markers in rheumatoid arthritis (RA).
Methods: Serum biochemical markers of bone formation (N-terminal propeptide of type I collagen, PINP and N-terminal midfragment of osteocalcin, N-MID.OC) and bone resorption (C-terminal telopeptide of type I collagen, CTX-I) were detected by chemiluminescence in 51 RA patients and 102 age and gender-matched healthy controls from Sun Yat-sen Memorial Hospital during the period of April 2010 to December 2012. Clinical and other serological parameters of reflecting RA activity and severity were collected and correlated with bone metabolism markers. TRAF6 was stained immunohistochemically in synovium from 30 active RA patients and the intensity of TRAF6+ cells was analyzed semiquantitatively. Correlation between synovial TRAF6 expression and serum bone metabolism markers was analyzed.
Results: Serum CTX-I level was significantly higher in RA patients than healthy controls ((0.53 ± 0.33) × 10⁻³ vs (0.33 ± 0.16) × 10⁻³ g/L, P < 0.01). Serum PINP and N-MID. OC levels of RA patients were correlated negatively with morning stiffness (P < 0.05), Health Assessment Questionnaire (HAQ) score (P < 0.05) and pain visual analogue scales (VAS) score (P < 0.05). Serum PINP level of RA patients correlated positively with gripping power (r = 0.296, P < 0.05). TRAF6 expression was observed in lining and sublining area of RA synovium and a higher expression of TRAF6 was seen in patients with severe synovitis than those with mild synovitis. Significant correlation was found between synovial TRAF6 expression and serum PINP level (r = 0.381, P < 0.05), as well as serum N-MID.OC level (r = 0.345, P < 0.05).
Conclusion: Increased bone resorption and altered skeletal bone metabolism are present in RA. An elevated expression of synovial TRAF6 may be correlated with increased compensatory bone formation. And TRAF6 is probably involved in the pathogenesis of bone metabolism imbalance through modulating synovial inflammation in RA.