School/Hospital of Stomatology, Zhejiang Chinese Medical University, Hangzhou, PR China.
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, PR China.
J Clin Periodontol. 2022 Aug;49(8):814-827. doi: 10.1111/jcpe.13647. Epub 2022 Jun 22.
Emerging studies have shown that immune response to biomaterial implants plays a central role in bone healing. Ipriflavone is clinically used for osteoporosis. However, the mechanism of ipriflavone in immune response to implants in early stages of osseointegration remains unclear. In this study, we aimed to investigate the potential role of ipriflavone in early bone healing process and uncover the underlying mechanism.
We carried out histological examination as well as analysis of proinflammatory cytokines and NLRP3 inflammasome activation in a tibial implantation mouse model with intra-peritoneal injection of ipriflavone. In addition, we explored the mechanism of ipriflavone in the regulation of NLRP3 inflammasome activation in macrophages.
In vivo, ipriflavone ameliorated host inflammatory response related to NLRP3 inflammasome activation at implantation sites, characterized by reductions of inflammatory cell infiltration and proinflammatory cytokine interleukin-1β levels. Ipriflavone treatment also showed beneficial effects on early osseointegration. Further investigations of the molecular mechanism showed that the suppression of NLRP3 inflammasome acts upstream of NLRP3 oligomerization through abrogating the production of reactive oxygen species.
These results revealed an anti-inflammatory role of ipriflavone in NLRP3 inflammasome activation through improving mitochondrial function. This study provides a new strategy for the development of immune-regulated biomaterials and treatment options for NLRP3-related diseases.
新的研究表明，对生物材料植入物的免疫反应在骨愈合中起着核心作用。依普拉芬用于治疗骨质疏松症。然而，在骨整合的早期阶段，依普拉芬对植入物的免疫反应的机制尚不清楚。在这项研究中，我们旨在研究依普拉芬在早期骨愈合过程中的潜在作用，并揭示其潜在的机制。
我们通过腹腔注射依普拉芬在胫骨植入小鼠模型中进行了组织学检查以及促炎细胞因子和 NLRP3 炎性体激活的分析。此外，我们还探讨了依普拉芬在调节巨噬细胞中 NLRP3 炎性体激活中的作用机制。
体内，依普拉芬改善了与 NLRP3 炎性体激活相关的宿主炎症反应，其特征是炎症细胞浸润和促炎细胞因子白细胞介素-1β水平降低。依普拉芬治疗对早期骨整合也有有益的影响。进一步的分子机制研究表明，NLRP3 炎性体的抑制作用通过阻断活性氧的产生而上调 NLRP3 寡聚化的上游。
这些结果揭示了依普拉芬通过改善线粒体功能在 NLRP3 炎性体激活中发挥抗炎作用。本研究为免疫调节生物材料的开发和 NLRP3 相关疾病的治疗提供了新策略。
