类风湿关节炎患者滑膜TRAF6表达与血清骨代谢标志物的相关性

Correlation between synovial TRAF6 expression and serum bone metabolism markers in rheumatoid arthritis

目的了解类风湿关节炎（RA）患者滑膜肿瘤坏死因子受体相关因子6（TRAF6）表达及其与血清骨代谢标志物的相关性。方法2010年4月至2012年12月在中山大学孙逸仙纪念医院采用电化学发光法检测51例确诊RA患者和102例健康对照者的血清骨代谢标志物I型前胶原氨基端前肽（PINP）、骨钙素降解产物（N—MID．OC）和I型胶原C末端肽（CTX—I）的水平并分析其与临床疾病活动指标的相关性。免疫组化染色检测30例活动期RA患者滑膜TRAF6表达，评估TRAF6＋细胞数并分析其与骨代谢标志物之间的相关性。结果RA患者血清CTX—I水平明显高于健康对照组[（0．53±0．33）×10^-3比（0．33±0．16）×10^-3 g／L，P〈0．01]。RA患者血清PINP和N—MID．OC与晨僵时间、健康评估问卷HAQ评分、疼痛VAS评分呈负相关（P〈0．05）。RA患者血清PINP与双手平均握力呈正相关（r=0．296，P〈0．05）。RA滑膜衬里层和衬里下层均见TRAF6表达，且TRAF6表达在重度滑膜炎组高于轻度滑膜炎组。RA患者滑膜组织TRAF6表达与PINP和N—MID．OC呈正相关（r=0．381，0．345，P〈0．05）。结论RA患者存在骨吸收增加、骨代谢失衡，其滑膜TRAF6表达增加可能与RA代偿性骨形成增加有关，TRAF6可能通过介导滑膜炎症参与了RA的骨代谢失衡。

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.