title: Tanshinol Rescues the Impaired Bone Formation Elicited by Glucocorticoid Involved in KLF15 Pathway.
abstract: Decreased bone formation is responsible for the pathogenesis of glucocorticoid- (GC-) induced osteoporosis (GIO), while the mechanism remains to be elucidated. The aim was to investigate how natural antioxidant tanshinol attenuates oxidative stress and rescues impaired bone formation elicited by GC in Sprague-Dawley rats and in C2C12 cells and/or MC3T3-E1 cells. The results showed that tanshinol prevented bone loss and decreased biomechanical characteristics and suppressed reduction of biomarkers related to osteogenesis in GIO rats. Further study revealed that tanshinol reversed decrease of transcription activity of Osterix-luc and rescued impairment of osteoblastic differentiation and bone formation involved in induction of KLF15 mRNA. Meanwhile, tanshinol diminished inhibition of protein expression of β-catenin and Tcf4 and transcription activity of Tcf4-luc induced by GC, especially under conditions of KLF siRNA in vitro. Additionally, tanshinol attenuated increase of reactive oxygen species (ROS) generation, phosphorylation of p66(Shc) expression, TUNEL-positive cells, and caspase-3 activity elicited by KLF15 under conditions of GC. Taken together, the present findings suggest that tanshinol attenuated the decrease of bone formation and bone mass and bone quality elicited by GC involved in KLF15/Wnt signaling transduction and counteracted GC-evoked oxidative stress and subsequent cell apoptosis involved in KLF15/p66(Shc) pathway cascade.
authors.affiliation: Department of Pharmacology, Guangdong Key Laboratory for R&D of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong 524023, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Guangdong Key Laboratory for R&D of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong 524023, China.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Nephrology, Shenzhen Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong 518033, China.
authors.forename: Dongtao
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Guangdong Key Laboratory for R&D of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong 524023, China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Guangdong Key Laboratory for R&D of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong 524023, China.
authors.forename: Yuyu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Guangdong Key Laboratory for R&D of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong 524023, China.
authors.forename: Shiying
authors.initials: S
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, Guangdong Key Laboratory for R&D of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong 524023, China.
authors.forename: Tie
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Guangdong Key Laboratory for R&D of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong 524023, China.
authors.forename: Liao
authors.identifier: 0000-0002-1922-3066
authors.initials: L
authors.lastname: Cui
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D001862:Bone Resorption / Q000473:pathology / Q000517:prevention & control; D002109:Caffeic Acids / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging; D005938:Glucocorticoids / Q000633:toxicity*; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects*; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000209:etiology; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1 / Q000378:metabolism; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D002109:Caffeic Acids; D004268:DNA-Binding Proteins; D005938:Glucocorticoids; C520013:Klf15 protein, rat; D051741:Kruppel-Like Transcription Factors; D017382:Reactive Oxygen Species; C528035:Shc1 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; C491192:Tcf4 protein, rat; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051176:beta Catenin; C585969:tanshinol