title: Rhizoma Dioscoreae extract protects against alveolar bone loss in ovariectomized rats via microRNAs regulation.
abstract: The aim of this study was to evaluate the osteoprotective effect of aqueous Rhizoma Dioscoreae extract (RDE) on the alveolar bone of rats with ovariectomy-induced bone loss. Female Wistar rats underwent either ovariectomy or sham operation (SHAM). The ovariectomized (OVX) rats were treated with vehicle (OVX), estradiol valerate (EV), or RDE. After treatments, the bone mineral density (BMD) and the three-dimensional microarchitecture of the alveolar bone were analyzed to assess bone mass. Microarrays were used to evaluate microRNA expression profiles in alveolar bone from RDE-treated and OVX rats. The differential expression of microRNAs was validated using real-time quantitative RT-PCR (qRT-PCR), and the target genes of validated microRNAs were predicted and further analyzed using Ingenuity Pathway Analysis (IPA). The key findings were verified using qRT-PCR. Our results show that RDE inhibits alveolar bone loss in OVX rats. Compared to the OVX rats, the RDE-treated rats showed upregulated expression levels of 8 microRNAs and downregulated expression levels of 8 microRNAs in the alveolar bone in the microarray analysis. qRT-PCR helped validate 13 of 16 differentially expressed microRNAs, and 114 putative target genes of the validated microRNAs were retrieved. The IPA showed that these putative target genes had the potential to code for proteins that were involved in the transforming growth factor (TGF)-β/bone morphogenetic proteins (BMPs)/Smad signaling pathway (Tgfbr2/Bmpr2, Smad3/4/5, and Bcl-2) and interleukin (IL)-6/oncostatin M (OSM)/Jak1/STAT3 signaling pathway (Jak1, STAT3, and Il6r). These experiments revealed that RDE could inhibit ovariectomy-induced alveolar bone loss in rats. The mechanism of this anti-osteopenic effect in alveolar bone may involve the simultaneous inhibition of bone formation and bone resorption, which is associated with modulation of the TGF-β/BMPs/Smad and the IL-6/OSM/Jak1/STAT3 signaling pathways via microRNA regulation.
authors.affiliation: Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China. zzgtcm@163.com.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China. sdsg_sch_86@126.com.
authors.forename: Changheng
authors.initials: C
authors.lastname: Song
authors.affiliation: Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China. zfz13552961302@163.com.
authors.forename: Fangzhen
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China. xlh891201@sina.com.
authors.forename: Lihua
authors.initials: L
authors.lastname: Xiang
authors.affiliation: Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China. chenyj@163.com.
authors.forename: Yanjing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China. lei_ruo@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China. jh-p@163.com.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Pan
authors.affiliation: Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China. liuhong@163.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Science, Dalian University of Technology, Dalian 116024, China. gxiao@creighton.edu.|Functional Genomics and Proteomics Laboratory, Osteoporosis Research Center, Creighton University Medical Center, Omaha, NE 68131, USA. gxiao@creighton.edu.
authors.forename: Gary Guishan
authors.initials: GG
authors.lastname: Xiao
authors.affiliation: Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China. judahong@sohu.com.
authors.forename: Dahong
authors.initials: D
authors.lastname: Ju
mesh_terms: D016301:Alveolar Bone Loss / Q000178:diet therapy* / Q000378:metabolism; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D027742:Dioscorea; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism; D053613:Janus Kinase 1 / Q000378:metabolism; D035683:MicroRNAs / Q000187:drug effects* / Q000378:metabolism; D053683:Oncostatin M / Q000378:metabolism; D010052:Ovariectomy / Q000009:adverse effects; D008517:Phytotherapy / Q000379:methods*; D028321:Plant Preparations / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D015850:Interleukin-6; D035683:MicroRNAs; D028321:Plant Preparations; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D016212:Transforming Growth Factor beta; D053683:Oncostatin M; D004958:Estradiol; C507906:Jak1 protein, rat; D053613:Janus Kinase 1