Abstract：
OBJECTIVE: The current study was performed to investigate the potential association of serum CXCL12 with disease severity in non-traumatic ONFH.
METHODS: This study enrolled 182 patients with non-traumatic ONFH and 182 age- and gender-matched healthy controls. The CXCL12 levels in serum were measured by enzyme-linked immunosorbent assay. Meanwhile, serum levels of procollagen type I (PINP) and Interleukin-33(IL-33) were also detected. The radiographic severity was determined by FICAT grade. Clinical severity was evaluated by visual analogue scale (VAS), Harris Hip Score (HHS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Among the non-traumatic ONFH, 90 patients ONFH received total hip arthroplasty, the localization and expression of the CXCL12 protein and mRNA were detected by immunohistochemistry, Western blot analysis, RT-PCR and in necrotic area and adjacent non-necrotic area from lesioned femoral neck from ONFH patients and healthy femoral head from femoral neck fracture patients. Receiver operating characteristic (ROC) curve analysis was carried out to confirm the diagnostic value serum CXCL12, PINP and IL-33 with regard to the FICAT grade.
RESULTS: Serum CXCL12 levels were significantly lower in non-traumatic ONFH patients compared with healthy controls. CXCL12 mRNA and protein expressions were both significantly decreased in necrotic area in comparison with non-necrotic area and healthy femoral head. Serum CXCL12 concentrations were drastically reduced in patients with FICAT stage 4 compared with stage 3, and CXCL12 concentrations in patients with stage 3 were markedly lower than stage 2. Serum CXCL12 levels were negatively related to FICAT grading. In addition, Serum CXCL12 concentrations were also negatively related to VAS, WOMAC scores and positively correlated with HHS scores. Meanwhile, serum CXCL12 levels were positively correlated with serum PINP and negatively correlated with IL-33 levels. ROC curve analysis implicated that decrease CXCL12 in serum may act as a favorable marker for FICAT grade.
CONCLUSIONS: Decreased serum CXCL12 concentrations may reflect disease severity of non-traumatic ONFH.
METHODS: This study enrolled 182 patients with non-traumatic ONFH and 182 age- and gender-matched healthy controls. The CXCL12 levels in serum were measured by enzyme-linked immunosorbent assay. Meanwhile, serum levels of procollagen type I (PINP) and Interleukin-33(IL-33) were also detected. The radiographic severity was determined by FICAT grade. Clinical severity was evaluated by visual analogue scale (VAS), Harris Hip Score (HHS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Among the non-traumatic ONFH, 90 patients ONFH received total hip arthroplasty, the localization and expression of the CXCL12 protein and mRNA were detected by immunohistochemistry, Western blot analysis, RT-PCR and in necrotic area and adjacent non-necrotic area from lesioned femoral neck from ONFH patients and healthy femoral head from femoral neck fracture patients. Receiver operating characteristic (ROC) curve analysis was carried out to confirm the diagnostic value serum CXCL12, PINP and IL-33 with regard to the FICAT grade.
RESULTS: Serum CXCL12 levels were significantly lower in non-traumatic ONFH patients compared with healthy controls. CXCL12 mRNA and protein expressions were both significantly decreased in necrotic area in comparison with non-necrotic area and healthy femoral head. Serum CXCL12 concentrations were drastically reduced in patients with FICAT stage 4 compared with stage 3, and CXCL12 concentrations in patients with stage 3 were markedly lower than stage 2. Serum CXCL12 levels were negatively related to FICAT grading. In addition, Serum CXCL12 concentrations were also negatively related to VAS, WOMAC scores and positively correlated with HHS scores. Meanwhile, serum CXCL12 levels were positively correlated with serum PINP and negatively correlated with IL-33 levels. ROC curve analysis implicated that decrease CXCL12 in serum may act as a favorable marker for FICAT grade.
CONCLUSIONS: Decreased serum CXCL12 concentrations may reflect disease severity of non-traumatic ONFH.
摘要：
目的：本研究旨在探讨非创伤性ONFH患者血清CXCL12与疾病严重程度的潜在关联。
方法：本研究纳入182例非创伤性ONFH患者和182例年龄和性别匹配的健康对照。采用酶联免疫吸附法测定血清中CXCL12水平。同时,还检测了I型前胶原（PINP）和白介素33（IL-33）的血清水平。射线照相严重程度由FICAT等级确定。采用视觉模拟评分法(VAS)评价临床严重程度,哈里斯髋关节评分（HHS）和西安大略省和麦克马斯特大学骨关节炎指数（WOMAC）。在非创伤性ONFH中，90例ONFH患者接受全髋关节置换术，免疫组化检测CXCL12蛋白和mRNA的定位和表达,蛋白质印迹分析,RT-PCR和ONFH患者的病变股骨颈坏死区和邻近的非坏死区以及股骨颈骨折患者的健康股骨头。进行受试者工作特征（ROC）曲线分析，以确认血清CXCL12，PINP和IL-33相对于FICAT等级的诊断价值。
结果：非创伤性ONFH患者血清CXCL12水平明显低于健康对照组。与非坏死区和健康股骨头相比，坏死区CXCL12mRNA和蛋白表达均显着降低。与3期相比，FICAT4期患者的血清CXCL12浓度显着降低，而3期患者的CXCL12浓度显着低于2期。血清CXCL12水平与FICAT分级呈负相干。此外,血清CXCL12浓度也与VAS呈负相干，WOMAC评分与HHS评分呈正相关。同时,血清CXCL12水平与血清PINP呈正相关,与IL-33水平呈负相关。ROC曲线分析暗示血清中CXCL12的减少可能充当FICAT等级的有利标志物。
结论：血清CXCL12浓度降低可能反映了非创伤性ONFH的疾病严重程度。
方法：本研究纳入182例非创伤性ONFH患者和182例年龄和性别匹配的健康对照。采用酶联免疫吸附法测定血清中CXCL12水平。同时,还检测了I型前胶原（PINP）和白介素33（IL-33）的血清水平。射线照相严重程度由FICAT等级确定。采用视觉模拟评分法(VAS)评价临床严重程度,哈里斯髋关节评分（HHS）和西安大略省和麦克马斯特大学骨关节炎指数（WOMAC）。在非创伤性ONFH中，90例ONFH患者接受全髋关节置换术，免疫组化检测CXCL12蛋白和mRNA的定位和表达,蛋白质印迹分析,RT-PCR和ONFH患者的病变股骨颈坏死区和邻近的非坏死区以及股骨颈骨折患者的健康股骨头。进行受试者工作特征（ROC）曲线分析，以确认血清CXCL12，PINP和IL-33相对于FICAT等级的诊断价值。
结果：非创伤性ONFH患者血清CXCL12水平明显低于健康对照组。与非坏死区和健康股骨头相比，坏死区CXCL12mRNA和蛋白表达均显着降低。与3期相比，FICAT4期患者的血清CXCL12浓度显着降低，而3期患者的CXCL12浓度显着低于2期。血清CXCL12水平与FICAT分级呈负相干。此外,血清CXCL12浓度也与VAS呈负相干，WOMAC评分与HHS评分呈正相关。同时,血清CXCL12水平与血清PINP呈正相关,与IL-33水平呈负相关。ROC曲线分析暗示血清中CXCL12的减少可能充当FICAT等级的有利标志物。
结论：血清CXCL12浓度降低可能反映了非创伤性ONFH的疾病严重程度。
