高迁移率族蛋白1促进股骨头塌陷的机制研究

Osteonecrosis of femoral head (ONFH) is a refractory disease in field of Orthopaedics. Its mechanism has not been completely clarified. Pathological exam was performed in patients of ONFH, and we found more immunocytes in the necrosis area than it was in patents of osteoarthritis. Immunohistochemistry staining were performed and we found that hmgb1 protein were focused more in necrotic area. Literature suggests that high mobility group box 1 (HMGB1) plays an important role in collapse of necrosis of the femoral head. In the process of ONFH, weight-bearing area of bone tissue necrosis releasing HMGB1, which promotes the proliferation and maturation of osteoclasts. The mechanism of HMGB1 promoting bone resorption of osteoclasts is likely to be realized through the phosphorylation of MEK pathway. Meanwhile, HMGB1 promoting osteoclast differentiation and maturation is enhanced by receptor-activating factor nuclear factor Kappa b (RANK); however, the mechanism is not clear. The possible mechanism is that RANK the disarmament of heme oxygenase 1 (HO-1) which is an inhibition of MEK. We suppose to establish rabbit model of ONFH. We focus on mechanism of HMGB1 on osteoclasts. We intend to suppress phosphate of MEK pathway by Lentivirus, which specific blocks the effect of HMGB1.

股骨头坏死是骨科常见的难治性疾病，发病机制尚未完全阐明。我们对股骨头坏死患者的股骨头组织进行病理检测，发现股骨头坏死区免疫细胞多于正常股骨头组织；免疫组织化学染色发现，坏死区表达较多hmgb1蛋白。文献提示高迁移率族蛋白1(HMGB1)基因在股骨头坏死塌陷过程起到关键作用。骨组织坏死后释放hmgb1促进破骨细胞的增殖和成熟。HMGB1促进破骨细胞骨吸收功能的可能机制是通过MEK通路磷酸化实现的。HMGB1在核因子κB受体活化因子（RANK）的辅助下增强破骨细胞分化和成熟，其机制尚不清楚，可能的机制是RANK解除血红素加氧酶1（HO-1）对MEK的抑制作用。我们拟建立兔股骨头坏死模型，研究HMGB1作用于破骨细胞的具体机制；拟制采用慢病毒沉默技术，阻断MEK等信号通路的传导，降低HMGB1对破骨细胞激活的生物效应。

1..发现DCK是激素性股骨头坏死的关键调控基因，其调控TBPL1和USF3在激素性股骨头坏死进展中起到关键作用。.2..CRNDE组合体减弱OS细胞增殖和侵袭并诱导凋亡和G0 /G1阻滞： CRNDE促进了糖原合酶激酶3β的磷酸化，从而激活Wnt /β-catenin途径；结果lncRNA CRNDE作为致癌基因，确实促进了OS的增殖，侵袭和上皮-间质转化，这表明lncRNACRNDE可能是OS的有效治疗靶标。.3..薯蓣皂苷引发了gsdme依赖的细胞死亡的焦亡，并且GSDME-N是由caspase-3生成的。我们的研究结果表明，薯蓣皂苷元可通过JNK/p38通路和gsdme依赖性焦亡诱导OS细胞凋亡，是一种潜在的治疗该疾病的药物。