中华骨质疏松和骨矿盐疾病杂志2023，Vol.16Issue(5)：458-467,10.DOI:10.3969/j.issn.1674-2591.2023.05.006
骨细胞程序性坏死对绝经后骨质疏松症患者脆性骨折的影响
Effects of osteocytes necroptosis on fragility fracture in patients with postmenopausal osteoporosis
摘要
Abstract
Objective To explore the impact of osteocytes necroptosis in fragility fracture of patients with postm-enopausal osteoporosis(PMOP),and further improve the pathogenesis of PMOP.Methods The clinical data and bone tissue samples of patients with femoral neck fragility fracture due to PMOP in the First Affiliated Hospital of Hainan Medi-cal University from January 2020 to January 2021 were collected.TUNEL+receptor interaction protein kinase(RIP)3 immunofluorescence was used to detect the number of necroptotic osteocytes in bone tissue.The expressions of necroptotic marker proteins RIP1,RIP3,mixed lineage kinase domain-like(MLKL),and apoptotic marker protein cleaved caspase-3 were detected by immunofluorescence and immunohistochemistry,and compare the differences between the two groups.The morphological changes of osteocyte were observed by transmission electron microscope.Reconstruction of microstructure of ward's triangle bone of femur by Micro-CT.Pearson correlation test was used to analyze the correlation between the rate of osteocyte necroptosis and microstructure of bone tissue.Results The results of immunofluorescence and immunohistochemistry showed:RIP1,RIP3,MLKL,and cleaved caspase-3 proteins were expressed in the cytoplasm of osteocytes in PMOP patients with fragility fracture of femoral neck,and the percentages of TUNEL+/RIP3+positive cells(necroptotic cells)(19.97%±1.83%vs.5.12%±0.29%)and TUNEL+/cleaved caspase-3+positive cells(apop-totic cells)(17.18%±1.32%vs.3.26%±0.41%)were significantly higher than those in control group(P＜0.01).The percentage of RIP1,RIP3,MLKL(49.38%±2.87%,26.12%±4.13%,29.63%±1.23%)were detected by immuno-histochemistry were significantly higher than those in the normal bone mass group(23.36%±1.25%,6.74%±0.96%,7.96%±0.42%)(P＜0.01).Under transmission electron microscopy,we found that osteocytes in patients with PMOP femoral neck fragility fracture showed typical morphological characteristics of necrosis.The bone loss of ward's triangle in PMOP patients with fragility fracture of femoral neck fracture was significantly higher than that in control group(P＜0.01).That is,bone mineral density,TB.Th,and TB.N were lower than those in control group[(725.63±10.17)g/cm3vs.(775.19±11.26)g/cm3,(0.13±0.01)mm vs.(0.16±0.02)mm,(1.35±0.04)mm-1vs.(1.52±0.07)mm-1](P＜0.01),but TB.SP was more than that in control group[(0.73±0.15)mm vs.(0.61±0.21)mm](P＜0.01).Pearson correlation analysis showed that osteocytes necroptosis was negatively correlated with bone mineral density,TB.Th,and TB.N(P＜0.01).Conclusion Osteocytes necroptosis does occur in postmenopausal patients with fragility fracture of femoral neck,and necroptotic osteocytes might play a more significant role mediating the loss of osteocytes and fragility fracture of femoral neck.关键词
绝经后骨质疏松/脆性骨折/程序性坏死/骨细胞/受体相关蛋白激酶3Key words
postmenopausal osteoporosis/fragility fracture/necroptosis/osteocyte/receptor interaction protein 3分类
医药卫生引用本文复制引用
崔红旺,苏天,温鹏,黎祥涛,陈丽英,付昆..骨细胞程序性坏死对绝经后骨质疏松症患者脆性骨折的影响[J].中华骨质疏松和骨矿盐疾病杂志,2023,16(5):458-467,10.基金项目
海南省重点研发计划(ZDYF2021SHFZ084) （ZDYF2021SHFZ084）
