title: Stimulation of Wnt/β-Catenin Signaling to Improve Bone Development by Naringin via Interacting with AMPK and Akt.
abstract: OBJECTIVE
  Naringin is a naturally existing compound in citrus fruits and has been elucidated to promote bone development and maintenance.
  
  
  METHODS
  The biological roles of naringin were investigated in vitro using osteoblast-like UMR-106 cells, and in vivo through performing ovariectomy to mimic osteoporosis in female mice. Since Wnt/β-catenin signaling is involved in osteoblastogenesis, the effect of naringin on Wnt/β-catenin signaling was studied.
  
  
  RESULTS
  Naringin promoted the mRNA and protein expressions of β-catenin, and improved Ser552 phosphorylation on β-catenin in UMR-106 cells, which leads to the activation of lymphoid enhancer factor (LEF)/ T-cell factor (TCF) transcription factors. The recruitments of protein kinase B (Akt) inhibitor (Akti-1/2) and AMP-activated protein kinase (AMPK) inhibitor (Dorsomorphin) reduced the influence of naringin on β-catenin phosphorylation, suggesting naringin activates β-catenin via regulating Akt and AMPK. In ovariectomized (OVX) mice naringin treatment improved the bone strength while AMPK and Akt inhibitors partly reversed the effect, which further proved the involvements of Akt and AMPK in the action of naringin in vivo.
  
  
  CONCLUSIONS
  Our study points to a novel finding on the mechanism of naringin in facilitating bone formation via Akt and AMPK signaling.
authors.affiliation: Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Wang
authors.forename: Wenpu
authors.initials: W
authors.lastname: Ma
authors.forename: Fu
authors.initials: F
authors.lastname: Wang
authors.forename: Jinlei
authors.initials: J
authors.lastname: Dong
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.forename: Bomin
authors.initials: B
authors.lastname: Wang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D002460:Cell Line; D002957:Citrus / Q000737:chemistry; D005260:Female; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D051820:TCF Transcription Factors / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D044950:Flavanones; D012333:RNA, Messenger; D051820:TCF Transcription Factors; D051176:beta Catenin; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; C005274:naringin