1. Activation of PGC-1α-dependent mitochondrial biogenesis supports therapeutic effects of silibinin against type I diabetic periodontitis
- Author
-
Xiaoyu Sun, Yifan Ping, Xumin Li, Yixin Mao, Yang Chen, Lixi Shi, Xinhua Hong, Liang Chen, Shuhong Chen, Zelin Cao, Pan Chen, Zhongchen Song, Daniel Wismeijer, Gang Wu, Yinhui Ji, Shengbin Huang, Oral Implantology, Maxillofacial Surgery (AMC + VUmc), Oral Regenerative Medicine (ORM), and Oral Cell Biology
- Subjects
silibinin ,peroxisome proliferator-activated receptor gamma-coactivator 1-alpha (PGC-1α) ,mitochondrial biogenesis ,diabetic periodontitis ,Periodontics - Abstract
Aim: To investigate whether silibinin impacts diabetic periodontitis (DP) via mitochondrial regulation. Materials and Methods: In vivo, rats were divided into control, diabetes, DP and DP combined with silibinin groups. Diabetes and periodontitis were induced by streptozocin and silk ligation, respectively. Bone turnover was evaluated by microcomputed tomography, histology and immunohistochemistry. In vitro, human periodontal ligament cells (hPDLCs) were exposed to hydrogen peroxide (H2O2) with or without silibinin. Osteogenic function was analysed by Alizarin Red and alkaline phosphatase staining. Mitochondrial function and biogenesis were investigated by mitochondrial imaging assays and quantitative polymerase chain reaction. Activator and lentivirus-mediated knockdown of peroxisome proliferator-activated receptor gamma-coactivator 1-alpha (PGC-1α), a critical regulator of mitochondria biogenesis, was used to explore the mitochondrial mechanisms. Results: Silibinin attenuated periodontal destruction and mitochondrial dysfunction and enhanced mitochondrial biogenesis and PGC-1α expression in rats with DP. Meanwhile, silibinin promoted cell proliferation, osteogenesis and mitochondrial biogenesis and increased the PGC-1α level in hPDLCs exposed to H2O2. Silibinin also protected PGC-1α from proteolysis in hPDLCs. Furthermore, both silibinin and activator of PGC-1α ameliorated cellular injury and mitochondrial abnormalities in hPDLCs, while knockdown of PGC-1α abolished the beneficial effect of silibinin. Conclusions: Silibinin attenuated DP through the promotion of PGC-1α-dependent mitochondrial biogenesis.
- Published
- 2023
- Full Text
- View/download PDF