不同剂量钙敏感受体抑制剂对磨损颗粒诱导小鼠骨溶解及炎症因子表达的影响

摘要
图/表
参考文献(22)
相关文章 (1)

全文: PDF (1220 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要目的观察不同剂量钙敏感受体抑制剂对磨损颗粒诱导的骨溶解及炎症因子表达的影响，从而探讨其防治人工关节无菌性松动的作用。方法将40 只8～10 周龄C57BL/6J 雄性小鼠采用随机数字表法分成空白对照组、颗粒组、低剂量组、高剂量组，每组10 只。颗粒组、低剂量组、高剂量组小鼠建立磨损颗粒诱导骨溶解颅骨模型，空白对照组进行假手术处理。术后第2 天开始，低剂量组、高剂量组小鼠分别隔日给予0.2、2.0 mg/kg 钙敏感受体抑制剂NPS2390 腹腔注射进行干预；空白对照组、颗粒组给予等量生理盐水替代。14 d 后，取颅骨标本，比较各组间颅骨骨矿物质密度、骨体积分数、骨孔隙率、颅骨骨面积、破骨细胞数量及炎症因子肿瘤坏死因子-α（TNF-α）和白介素-1β（IL-1β）表达量。结果颗粒组破骨细胞数、骨孔隙率、炎症因子TNF-α 和IL-1β 表达量高于空白对照组，而颅骨骨矿物质密度、骨体积分数及骨面积低于空白对照组，差异有统计学意义（P＜0.05）。低剂量组骨矿物质密度高于颗粒组，破骨细胞数、炎症因子TNF-α 和IL-1β 表达量低于颗粒组，差异有统计学意义（P＜0.05）。高剂量组颅骨骨矿物质密度、骨体积分数及骨面积高于颗粒组，颅骨骨孔隙率、破骨细胞数、炎症因子TNF-α 和IL-1β表达量低于颗粒组，差异有统计学意义（P＜0.05）。高剂量组的颅骨骨矿物质密度和骨体积分数高于低剂量组，破骨细胞数及炎症因子TNF-α 和IL-1β 表达量低于低剂量组，差异有统计学意义（P＜0.05）。结论敏感受体抑制剂（NPS2390）可有效抑制磨损颗粒诱导的骨溶解及炎症因子表达，为人工关节无菌性松动防治提供新思路。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章

关键词 ：钙敏感受体, NPS2390, 磨损颗粒, 骨溶解, 人工关节, 无菌性松动

Abstract：

Objective To observe the effects of different doses of calcium-sensing receptor inhibitors on the osteolysis and the expression inflammatory factor induced by wear particles, so as to investigate its effect of preventing aseptic loosening of artificial joints. Methods Forty C57BL/6J male mice aged 8-10 weeks were divided into control group,particle group, low dose group and high dose group according to the random number table, with 10 mice in each group.Wear particle-induced mouse calvaria osteolysis model were established in the particle group, low-dose group and high-dose group, then the control group was treated with sham operation. From the second day after operation, mice in low-dose group and high-dose group were given 0.2 mg/kg and 2.0 mg/kg NPS2390 intraperitoneally every other day.The control group and particle group were replaced by the same amount of normal saline. After 14 days, the skull specimens were taken and the skull bone mineral density, bone volume fraction, bone porosity, skull bone area, the number of osteoclast and the expression of the inflammatory factor tumor necrosis factor-α (TNF-α) and interleukin-1β(IL-1β) were compared between the groups. Results In particle group, the number of osteoclasts, the bone porosity and the expression of inflammatory factor TNF-α and IL-1β were higher than that in control group,however,the bone mineral density,the bone volume fraction,and the bone area of the skull in particle group were lower than those of control group,the differences were statistically significant (P＜0.05). In low dose group, the bone mineral density was higher than that in particle group, the number of osteoclast and the expression of inflammatory factor TNF-α and IL-1β in low dose group were lower than those in the particle group, the differences were statistically significant (P＜0.05). The bone mineral density, bone volume fraction and bone area of the high-dose group were higher than those of the granule group, while the bone porosity, the number of osteoclasts, the expression of inflammatory factors TNF-α and IL-1β were lower than those of the granule group, the differences were statistically significant(P＜0.05).The bone mineral density and bone volume fraction of the high dose group were higher than those of the low dose group, and the number of osteoclasts and the expression of inflammatory factors TNF-α and IL-1β were lower than those of the low dose group,and the differences were statistically significant (P＜0.05).Conclusion The calcium-sensing receptor inhibitor (NPS2390) can effectively inhibit osteolysis and the expression of inflammatory induced by wear particles, and provides new ideas for prevention aseptic loosening of artificial joints.

Key words： Calcium-sensing receptor NPS2390 Wear particle Osteolysis Artificial prosthesis Aseptic loosening

基金资助:江西省卫生健康委科技计划项目（20204524）；
江西省教育厅科技青年项目（GJJ170883）；
江西省教育厅科技计划项目（GJJ14678）；
江西省赣州市指导性科技计划项目（GZ2020ZSF041）。

引用本文:

钟艳春；叶勇军；刘午阳. 不同剂量钙敏感受体抑制剂对磨损颗粒诱导小鼠骨溶解及炎症因子表达的影响[J]. 中国当代医药, 2022, 29(26): 5-10转15.
ZHONG Yanchun YE Yongjun LIU Wuyang. Effect of different doses of calcium-sensing receptor inhibitors on the osteolysis and the expression inflammatory factor induced by wear particles in mice. 中国当代医药, 2022, 29(26): 5-10转15.

链接本文:

https://www.dangdaiyiyao.com/CN/ 或 https://www.dangdaiyiyao.com/CN/Y2022/V29/I26/5

[1]	Goodman SB，Gallo J.Periprosthetic Osteolysis：Mechanisms，Prevention and Treatment[J].J Clin Med，2019，8（12）：2091.
[2]	Sundararaman SS，van der Vorst EPC.Calcium-Sensing Receptor （CaSR），Its Impact on Inflammation and the Consequences on Cardiovascular Health[J].Int J Mol Sci，2021，22（5）：2478.
[3]	Klein GL，Castro SM，Garofalo RP.The calcium-sensing receptor as a mediator of inflammation[J].Semin Cell Dev Biol，2016，49：52-56.
[4]	Klein GL.The Role of Calcium in Inflammation-Associated Bone Resorption[J].Biomolecules，2018，8（3）：69.
[5]	戴闽，钟艳春，宗凌，等.VEGF 抗体抑制磨损颗粒诱导骨溶解的实验研究[J].中国修复重建外科杂志，2012，26（6）：647-651.
[6]	李朋，杨淑野，张锴，等.不同磨损颗粒对体外培养人外周血单核细胞的影响[J].中国组织工程研究，2019，23（6）：894-900.
[7]	刘子歌，刘洋，张晨，等.巨噬细胞对钛和钴铬钼颗粒吞噬差异性的研究[J].中华实验外科杂志，2021，38（7）：1231-1233.
[8]	席向东，陈德胜，杨超，等.MMP-9、TNF-α、IL-1 在无菌性松动界膜组织中的表达及相关性研究[J].生物骨科材料与临床研究，2021，18（1）：5-8，12.
[9]	Mitchell W，Bridget MJ，Stone MH，et al.Comparison of the response of human peripheral blood mononuclear cells to challenge with particles of three bone cements in vitro[J].Biomaterials，2003，24（5）：737-748.
[10]	D′Espessailles A，Santillana N，Sanhueza S，et al.Calcium sensing receptor activation in THP-1 macrophages triggers NLRP3 inflammasome and human preadipose cell inflammation[J].Mol Cell Endocrinol，2020，501：110654.
[11]	Jager E，Murthy S，Schmidt C，et al.Calcium-sensing receptor-mediated NLRP3 inflammasome response to calciprotein particles drives inflammation in rheumatoid arthritis[J].Nat Commun，2020，11（1）：4243.
[12]	Su Y，Zhang Y，Hu Z，et al.Prokineticin 2 via Calcium-Sensing Receptor Activated NLRP3 Inflammasome Pathway in the Testicular Macrophages of Uropathogenic Escherichia coli-Induced Orchitis[J].Front Immunol，2020，11：570872.
[13]	Lee JW，Park HA，Kwon OK，et al.NPS 2143，a selective calcium-sensing receptor antagonist inhibits lipopolysaccharide-induced pulmonary inflammation[J].Mol Immunol，2017，90：150-157.
[14]	戴闽，程明，刘虎诚，等.不同浓度金属磨损颗粒对破骨细胞体外分化的影响[J].中国矫形外科杂志，2011，19（4）：316-319.
[15]	张晨，李燕，郭凤英，等.RANKL/RANK/OPG 信号通路调控磨损颗粒诱导的小鼠炎性骨溶解[J].中国医科大学学报，2021，50（2）：130-134，140.
[16]	Zhang L，Haddouti EM，Welle K，et al.The Effects of Biomaterial Implant Wear Debris on Osteoblasts[J].Front Cell Dev Biol，2020，8：352.
[17]	雷群，林东，黄文秀，等.钙离子对人成骨细胞迁移与成骨分化的影响[J].华西口腔医学杂志，2018，36（6）：602-608.
[18]	Ko1odziejska B，Stepień N，Kolmas J.The Influence of Strontium on Bone Tissue Metabolism and Its Application in Osteoporosis Treatment[J].Int J Mol Sci，2021，22（12）：6564.
[19]	Liu X，Zhu S，Cui J，et al.Strontium ranelate inhibits titanium-particle-induced osteolysis by restraining inflammatory osteoclastogenesis in vivo[J].Acta Biomater，2014，10（11）：4912-4918.
[20]	Liu L，Fan Y，Chen Z，et al.CaSR Induces Osteoclast Differentiation and Promotes Bone Metastasis in Lung Adenocarcinoma[J].Front Oncol，2020，10：305.
[21]	Boudot C，Hénaut L，Thiem U，et al.Overexpression of a functional calcium-sensing receptor dramatically increases osteolytic potential of MDA-MB-231 cells in a mouse model of bone metastasis through epiregulin-mediated osteoprotegerin downregulation[J].Oncotarget，2017，8（34）：56460-56472.
[22]	董冰子，孙晓方，邓玉杰，等.钙敏感受体拮抗剂溶钙素对小鼠骨密度和骨代谢的影响[J].精准医学杂志，2019，34（2）：139-142.