护骨素在强直性脊柱炎外周关节骨质破坏病理机制中的作用

目的检测护骨素(OPG)在强直性脊柱炎(AS)外周关节滑膜组织中的表达,并以类风湿关节炎(RA)、骨关节炎(OA)患者和健康志愿者外周关节滑膜组织为对照,了解OPG表达与AS患者外周关节骨质破坏病理改变的相关性。方法应用单克隆抗体,通过免疫组织化学方法检测13例AS、16例RA、17例OA及6名健康对照关节滑膜组织中OPG的表达及分布状况,并通过计算机辅助图像分析系统和半定量分析方法确定OPG在各滑膜组织中表达水平之间的差异,分析OPG表达与炎性指标及关节X线分期之间的相关性。结果OPG蛋白在所有13例AS滑膜组织中均有阳性表达,阳性细胞主要分布于滑膜衬里层、衬里下层区域,滑膜软骨交界区OPG表达明显低于滑膜衬里层和衬里下层;2名健康对照滑膜组织中有阳性表达,但明显低于AS患者组。RA及OA患者组未见OPG阳性表达。结论譹AS组滑膜组织中OPG表达水平明显高于健康对照组(P<0.01),而RA、OA滑膜组织中未见OPG表达,说明OPG的高水平表达是滑膜组织对炎症反应/关节破坏所特有的表现,OPG的局部表达是维持AS关节骨代谢稳定的重要因素,这可能是大多数AS患者外周关节受累预后好于RA的原因之一。譺AS患者组滑膜软骨交界区中OPG表达量显著减少可能是导致关节骨质破坏的重要原因,提示关节局部应用OPG治疗有可能改善受累关节的骨

The role of osteoprotegerin in the pathogenesis of peripheral joint bone destruction of ankylosing spondylitis

Objective To detect osteoprotegerin (OPG) protein levels in synovial tissues from ankylosing spondylitis (AS) patients and compare the expression level and distribution of OPG protein in AS, rheumatoid arthritis (RA), osteoarthritis (OA) and normal synovial tissues. By studying the correlation of OPG expressions with pathological changes of inflammatory joints to explore the role of OPG in the pathogenesis of bone destruction in AS. Methods Immunohistochemical analysis was performed using OPG monoclonal antibody to detect OPG expression in 13 AS, 16 RA,17 OA patients and 6 healthy controls. The labeled synovial tissue sections were quantified by digital image analysis and semiquantitively analyzed to compare the expression of OPG positve cells in different patient groups and normal subjects. In addition, the correlation of OPG expression with certain inflammatory indices (including ESR, CRP, blood platelet count) and radiological stage of involved joints was analyzed respectively. Results Positive staining of OPG was seen in all 13 AS patients. OPG expression was predominantly seen in the synovial lining layer and sublining areas. Positive staining of OPG was also found in the synovial tissues of 2 normal subjects, but the OPG level was significantly lower. No positive staining of OPG was found in synovial tissues from all patients with RA and OA. Conclusions {1}Higher levels of OPG are expressed in synovial tissues from AS patients than in tissues from normal subjects (P<0.01). No OPG is found in synovial tissues from patients with RA and OA, suggesting that OPG expression may be the consequence of synoviocytes reaction to inflammation and bone destruction and that OPG may have a protective effect on bone integrity. This serves a possible explanation for the better prognosis of the peripheral joint involvement in AS patients in comparison with RA patients. {2}Decrease in OPG levels at synovium-cartilage junctions is likely to be the main cause of bone destruction in AS patients. OPG may well have a therapeutic role in preventing bone destruction in AS.