Activation of PGC-1α-dependent mitochondrial biogenesis supports therapeutic effects of silibinin against type I diabetic periodontitis.

Abstract

To investigate whether silibinin impacts diabetic periodontitis (DP) via mitochondrial regulation. 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 (H2 O2 ) 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. 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 H2 O2 . 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. Silibinin attenuated DP through the promotion of PGC-1α-dependent mitochondrial biogenesis.