title: Silibinin alleviates high glucose-suppressed osteogenic differentiation of human bone marrow stromal cells via antioxidant effect and PI3K/Akt signaling.
abstract: High glucose is one of the possible causes for osteoporosis and fracture in diabetes mellitus. Our previous study showed that silibinin can increase osteogenic effect by stimulating osteogenic genes expression in human bone marrow stem cells (hBMSCs). However, no study has yet investigated the effect of silibinin on osteogenic differentiation of hBMSCs cultured with high glucose. The aim of this study was to evaluate the influence of high glucose on osteogenic differentiation of hBMSCs and to determine if silibinin can alleviate those effects. In this study, the hBMSCs were cultured in an osteogenic medium with physiological (normal glucose, NG, 5.5mM) or diabetic (high glucose, HG, 30mM). The effects of silibinin on HG-induced osteogenic differentiation were evaluated by alkaline phosphatas (ALP) activity assay, Von Kossa staining and real time-polymerase chain reaction. HG-induced oxidative damage was also assessed. Western blot were performed to examine the role of PI3K/Akt pathway. We demonstrated that HG suppressed osteogenic differentiation of hBMSCs, manifested by a decrease in expression of osteogenic markers and an increase of oxidative damage markers including reactive oxygen species and lipid peroxide (MDA). Remarkably, all of the observed oxidative damage and osteogenic dysfunction induced by HG were inhibited by silibinin. Furthermore, the PI3K/Akt pathway was activated by silibinin. These results demonstrate that silibinin may attenuate HG-mediated hBMSCs dysfunction through antioxidant effect and modulation of PI3K/Akt pathway, suggesting that silibinin may be a superior drug candidate for the treatment of diabetes related bone diseases.
authors.affiliation: Department of Orthopaedic Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: yingxiaozhou@sina.com.
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Ying
authors.affiliation: Department of Ultrasound Imaging, the First Affiliated Hospital of Wenzhou Medical University, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Orthopaedic Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Haixiao
authors.initials: H
authors.lastname: Liu
authors.affiliation: The Orthopaedic Department of Beilun People's Hospital, Ningbo 315800, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Nie
authors.affiliation: Department of Orthopaedic Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Shui
authors.affiliation: Department of Orthopaedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Orthopaedic Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Kehe
authors.initials: K
authors.lastname: Yu
authors.affiliation: Trauma Center of the Affiliated Hospital of Hainan Medical College, Haikou 570100, China.
authors.forename: Shaowen
authors.initials: S
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000633:toxicity*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D012838:Silymarin; D000077385:Silybin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose
keywords: Antioxidant; High glucose (HG); Osteoporosis; PI3K/Akt pathway; Silibinin