摘要目的:探讨金黄色葡萄球菌感染所致骨量丢失的分子机制。方法:将30只雄性8周龄C57BL/6小鼠随机分为3组（ n=10）：对照组、感染组及感染+JAK抑制剂（JAKi）组。造模2周后于股骨和胫骨处取材。通过Micro-CT重建并分析骨小梁体积分数(BV/TV)、骨小梁数量(Tb.N)、骨小梁厚度(Tb.Th)、骨小梁间距(Tb.Sp)以检测骨量改变；骨钙素免疫组化、Goldner三色染色用于定量成骨细胞；抗酒石酸磷酸酶（TRAP）染色用于定量破骨细胞；下载并分析GSE166522数据集探索金黄色葡萄球菌感染与骨细胞衰老及JAK/STAT通路的关系；Senescence β-Galactosidase、Osterix和P16免疫荧光共定位用于观察细胞衰老。 结果:MicroCT结果显示感染组目标区域松质骨的骨量较对照组显著丢失，骨钙素免疫组化、Goldner三色染色结果提示感染组的成骨细胞数量较对照组显著降低，以上比较差异均有统计学意义（ P<0.05）。TRAP染色提示感染组与对照组的破骨细胞数量变化差异无统计学意义（ P>0.05）。生物信息学分析发现金黄色葡萄球菌感染会引起骨细胞衰老且在感染条件下JAK/STAT通路被激活。Senescence β-Galactosidase染色提示感染组骨组织衰老细胞较对照组显著增多，Osterix和P16免疫荧光共定位提示感染组衰老的骨祖细胞数量较对照组显著增多，以上比较差异均有统计学意义（ P<0.05）。与感染组相比，感染+JAKi组衰老的骨祖细胞数量明显减少且骨量丢失得到了部分逆转。 结论:金黄色葡萄球菌通过JAK/STAT通路诱导骨祖细胞衰老并最终导致骨量丢失。

abstractsObjective:To explore the molecular mechanism for bone mass loss caused by staphylococcus aureus infection.Methods:Thirty 8-week-old male C57BL/6 mice were randomly divided into 3 groups ( n=10): control, infection and infection+JAK inhibitor (JAKi) ones. The mice were killed 2 weeks later for sampling from the femur and tibia. Micro-CT reconstruction was performed for analyses of BV/TV, Tb.N, Tb.Th and Tb.Sp to detect changes in bone mass; OCN immunohistochemistry and Goldner's trichrome staining were used to quantify osteoblasts; TRAP staining was used to quantify osteoclasts; the GSE166522 data set was downloaded and analyzed to explore the relationships between staphylococcus aureus infection and bone cell senescence and JAK/STAT pathway. Senescence β-Galactosidase staining, Osterix and P16 immunofluorescence colocalization were used to observe the changes in number of senescent cells. Results:MicroCT results showed a statistically significant difference in the loss of cancellous bone in the target area in the infection group compared with the control group ( P<0.05). The results of osteocalcin immunohistochemistry and Goldner's trichrome staining indicated that the number of osteoblasts in the infection group was significantly reduced ( P<0.05). TRAP staining indicated no significant difference in the number of osteoclasts between the infection and control groups ( P>0.05). Bioinformatics analysis found that staphylococcus aureus infection caused bone cell senescence and the JAK/STAT pathway was activated after the infection. Senescence β-Galactosidase staining suggested that senescent cells increased in the infection group compared with the control group. The number of Osterix and P16 positive senescent osteoprogenitor cells in the infection group was increased significantly compared with the control group. The number of senescent osteoprogenitor cells in the infection+JAKi group was significantly reduced and the bone loss was partially reversed after treatment of JAK inhibitor, compared with the infection group. Conclusion:Staphylococcus aureus may induce osteoprogenitor cell senescence through the JAK/STAT pathway and eventually lead to bone mass loss.