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脂多糖作用下MLO-Y4骨细胞力学生物学响应. (2025). 环球医学研究, 2(4), 8-17. https://doi.org/10.62836/
Copyright (c) 2025 刘力铭, 黄诗兰, 于浩洋, 刘泽, 郭勇
This work is licensed under a Creative Commons Attribution 4.0 International License.
脂多糖作用下MLO-Y4骨细胞力学生物学响应
刘力铭，黄诗兰，于浩洋，刘泽，郭勇*
桂林医科大学，广西桂林
摘要：目的：本研究旨在探讨脂多糖（LPS）作用下骨细胞的力学生物学响应及其机制。方法：以小鼠骨细胞MLO-Y4为对象，设置四组处理：对照组、LPS刺激组、力学刺激组（2500με、0.5Hz、1h/d、持续3天）及LPS+力学刺激组。检测指标包括细胞增殖活性、功能相关分子（NO、NOS、IGF-1、PGE2）及氧化应激指标（丙二醛和超氧化物含量）。结果：LPS组细胞增殖活性显著低于对照组，而力学刺激组显著升高；联合处理组较LPS组显著上升。在功能指标方面，LPS组各因子表达均低于对照组，力学刺激组均上升，联合组则显著高于LPS组。氧化应激水平方面，LPS组超氧化物和丙二醛含量均高于对照组，联合组则显著低于LPS组。结论：LPS明显抑制骨细胞增殖与功能， 并增强氧化应激；适宜的力学刺激不仅促进骨细胞增殖与功能，还能有效拮抗LPS的抑制作用，并在炎症条件下维持细胞功能。其机制与力学刺激增强骨细胞的抗氧化应激能力、减轻氧化损伤密切相关。本研究为理解力学刺激在炎症性骨病中的保护作用提供了细胞学依据。
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[22] 刘奇奇,刘敏,杨健,等.脂多糖刺激小鼠MLO-Y4骨细胞白细胞介素6及核因子κB受体活化因子配体的表达[J].中国组织工程研究, 2022,26(20): 3121-3126.
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[26] Zhang H, Liu L, Jiang C, et al. MMP9 protects against LPS-induced inflammation in osteoblasts[J]. Innate Immunity, 2020, 26(4): 259- 269.
[27] Saura M, Tarin C, Zaragoza C. Recent Insights into the Implication of Nitric Oxide in Osteoblast Differentiation and Proliferation during Bone Development[J]. The Scientific World Journal, 2010, 10: 624-632.
[28] Nakao Nobuhiko, Mori Izumi, Sunaga Junko, et al. Large magnitude of force leads to NO-mediated cell shrinkage in single osteocytes implying an initial apoptotic response[J]. Journal of Biomechanics, 2021, 117: 110245-110245.
[29] McGarry JG, Klein-Nulend J, Prendergast PJ.The effect of cytoskeletal disruption on pulsatile fluid flow-induced nitric oxide and prostaglandin E2 release in osteocytes and osteoblasts[J]. Biochemical and biophysical research communicatio ns,2005,330(1):341-348.
[30] Park J, Fertala A, Tomlinson ER. Naproxen impairs load-induced bone formation, reduces bone toughness, and diminishes woven bone formation following stress fracture in mice[J]. Bone, 2019, 124: 22-32.
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[2] 景达.正常和特殊力学环境下骨信号转导[J].医用生物力学,2024,39(S1):10-11.
[3] Rinaldo F, Silva DRGS, Estela S, et al. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells.[J]. BioMed research international, 2015, 2015421746.
[4] 杨全增, 张成俊, 姜金, 等. 骨细胞力学信号转导功能研究被引最高50 篇相关文献分析[J]. 中国骨质疏松杂志, 2017, 23(09): 1174-1179+1186.
[5] Huayue C, Takao S, Kin-ya K. The osteocyte plays multiple roles in bone remodeling and mineral homeostasis[J]. Medical molecular morphology, 2015, 48(2): 61-8.
[6] 杜静珂,于志锋.机体衰老对骨细胞力学响应的影响[J].医用生物力学,2019,34(03):333-338.
[7] 高瑞,辜洁,康迪斯,等.高糖对成骨细胞MC3T3-E1凋亡和氧化应激的影响[J].局解手术学杂志,2019,28(05):348-352.
[8] Wenqing L, Xudong W, Yongqiang D, et al. Mechanical stimuli-mediated modulation of bone cell function- implications for bone remodeling and angiogenesis [J]. Cell and tissue research, 2021, 386(3): 445-454.
[9] 徐又佳,林华,夏维波.重视机械负荷对骨细胞功能的影响[J].中华骨质疏松和骨矿盐疾病杂志,2023,16(02):93-101.
[10] 张晓音,吴旻,李雨萌,等.脂多糖的效应及其机理研究进展[J].动物医学进展,2015,36(12):133-136.
[11] 秦祎雄,袁子健,谢山周,等.茶多酚对脂多糖刺激下成骨细胞增殖分化的影响[J]. 中国组织工程研究, 2023, 27(35): 5665- 5669.
[12] 赵强,肖波,陈天逸,等.积雪草苷对脂多糖诱导的成骨细胞增殖和分化的影响[J]. 中国中医骨伤科杂志, 2024, 32(07): 24- 28+33.
[13] 杨焕.骨细胞力学响应RNA的筛选及成骨分化相关的生物信息学分析[D]. 桂林医学院, 2022.
[14] 唐占英,褚立希,胡志俊.力学刺激对膝骨关节炎软骨细胞作用的分子生物学机制进展[J]. 河北医学, 2019, 25(02): 332-335.
[15] Jun M, Zhu W, Jianquan Z, et al. Resveratrol Attenuates Lipopolysaccharides (LPS)-Induced Inhibition of Osteoblast Differentiation in MC3T3-E1 Cells[J]. Medical science monitor: international medical journal of experimental and clinical research, 2018, 24: 2045-2052.
[16] 张倩璐,江婷,赵国军.脂多糖抑制成骨细胞分化作用研究[J]. 中国临床药理学杂志,2019,35(21):2743-2746.
[17] Ke Y, Yuanyuan M, Xianxian L, et al. Lipopolysaccharide increases IL-6 secretion via activation of the ERK1/2 signaling pathway to up- regulate RANKL gene expression in MLO-Y4 cells[J]. Cell biology international, 2017, 41(1): 84-92.
[18] Chun G, Sheng-Li W, Song-Tao X, et al. SP600125 reduces lipopolysaccharide-induced apoptosis and restores the early-stage differentiation of osteoblasts inhibited by LPS through the MAPK pathway in MC3T3-E1 cells[J]. International journal of molecular medicine, 2015, 35(5): 1427-34.
[19] 余科,吴湘楠,刘文佳,等.LPS刺激小鼠骨细胞RANKL/OPG和IL-6表达的实验研究[J].口腔医学研究,2016,32(03):220-223.
[20] Sharma Kriti, Kumar Shiv, Prakash Ravi, Khanka Sonu,Mishra Tripti,Rathur Rajat... & Singh Divya. (2022). Chebulinic acid alleviates LPS-induced inflammatory bone loss by targeting the crosstalk between reactive oxygen species/NFκB signaling in osteoblast cells. Free radical biology & medicine, 194(2023): 99-113. doi:10.1016/j.freeradbiomed.2022.11.026.
[21] 李青,朱亦堃,焦玉睿.应激时多种调节因子对骨代谢及糖代谢的影响[J].新医学,2020,51(02):103-107.
[22] 刘奇奇,刘敏,杨健,等.脂多糖刺激小鼠MLO-Y4骨细胞白细胞介素6及核因子κB受体活化因子配体的表达[J].中国组织工程研究, 2022,26(20): 3121-3126.
[23] 陈则强,李昊.芒果苷对脂多糖诱导小鼠成骨细胞凋亡的影响及机制研究[J].当代医学,2021,27(04):87-89.
[24] XiangTao Z, Min S, Li Z, et al. The potential function of miR- 135b-mediated JAK2/STAT3 signaling pathway during osteoblast differentiation[J]. The Kaohsiung journal of medical sciences, 2020, 36(9): 673-681.
[25] Yongyong Y, Liping W, Linhu G, et al. Osteocyte-Mediated Translation of Mechanical Stimuli to Cellular Signaling and Its Role in Bone and Non-bone-Related Clinical Complications[J]. Current osteoporosis reports, 2020, 18(1): 67-80.
[26] Zhang H, Liu L, Jiang C, et al. MMP9 protects against LPS-induced inflammation in osteoblasts[J]. Innate Immunity, 2020, 26(4): 259- 269.
[27] Saura M, Tarin C, Zaragoza C. Recent Insights into the Implication of Nitric Oxide in Osteoblast Differentiation and Proliferation during Bone Development[J]. The Scientific World Journal, 2010, 10: 624-632.
[28] Nakao Nobuhiko, Mori Izumi, Sunaga Junko, et al. Large magnitude of force leads to NO-mediated cell shrinkage in single osteocytes implying an initial apoptotic response[J]. Journal of Biomechanics, 2021, 117: 110245-110245.
[29] McGarry JG, Klein-Nulend J, Prendergast PJ.The effect of cytoskeletal disruption on pulsatile fluid flow-induced nitric oxide and prostaglandin E2 release in osteocytes and osteoblasts[J]. Biochemical and biophysical research communicatio ns,2005,330(1):341-348.
[30] Park J, Fertala A, Tomlinson ER. Naproxen impairs load-induced bone formation, reduces bone toughness, and diminishes woven bone formation following stress fracture in mice[J]. Bone, 2019, 124: 22-32.
[31] 阴健,浩志超,廖爽,等.间歇性加载周期性压力增加骨细胞分泌一氧化氮和前列腺素E2[J].生物医学工程学杂志,2014,31(03):619-624.
[32] Ziyi W, Yoshihito I, Takanori I, et al. Screening of key candidate genes and pathways for osteocytes involved in the differential response to different types of mechanical stimulation using a bioinformatics analysis[J]. Journal of bone andmineral metabolism, 2019, 37(4): 614-626.
[33] Minjie L, Zhongyuan T, Chengfei Z, et al. Lipopolysaccharides Affect Compressed Periodontal Ligament Cells via Eph-ephrin Signaling[J]. Oral diseases, 2021, 28(6): 1662-1673.
[34] Alaa A, Rhodanne L, Fahd A. High-Glucose Media Reduced the Viability and Induced Differential Pro-Inflammatory Cytokines in Human Periodontal Ligament Fibroblasts[J]. Biomolecules, 2023, 13(4): 690.
[35] Shinsuke A, Daigo Y, Shirou T, et al. Zoledronate and lipopolysaccharide suppress osteoblast differentiation through downregulating phosphorylation of Smad in pre-osteoblastic MC3T3-E1 cells[J]. Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, 2022, 34(4): 472-479.
[36] 章家皓,刘予豪,周驰,等.氧化应激促进成骨细胞铁死亡介导激素性股骨头坏死的病理过程[J].中国组织工程研究,2024,28(20):3202-3208.