title: Glucocorticoid-induced leucine zipper may play an important role in icariin by suppressing osteogenesis inhibition induced by glucocorticoids in osteoblasts.
abstract: OBJECTIVE
  Icariin is a potent stimulator of osteogenic differentiation; however, the mechanism underlying its osteogenic effect remains unclear. The osteogenic effect of icariin is related to the upstream glucocorticoid-induced leucine zipper (GILZ) signaling pathway, and antagonism with dexamethasone-induced osteoblast inhibition was noted.
  
  
  METHODS
  MC3T3-E1 cells were cultured in induced medium treated with icariin with or without dexamethasone. After short interfering RNA (siRNA) were used to silence GILZ expression, the degree of mineralization, proliferation, and GILZ expression as well as the levels of osteogenic (OPG, RANKL, ALP, OC and RUNX2) markers were tested.
  
  
  RESULTS
  Dexamethasone inhibited, while icariin increased, osteogenic activity, as indicated by ALP activity and calcium nodules. Meanwhile, dexamethasone dose-dependently (10-6M-10-4M) increased GILZ and RANKL expression and reduced ALP, OPG and OC, but the pattern of mRNA expression was reversed when icariin was added. Furthermore, GILZ (dexamethasone-induced) inhibition caused by icariin or moderately silenced by GILZ siRNA abolished the osteogenesis inhibition effect of dexamethasone, as indicated by the changes in the GILZ, ALP, OPG and RANKL expression levels; ALP activity; and calcium nodule.
  
  
  CONCLUSIONS
  These results indicate that the GILZ-mediated osteogenic signal pathway is involved in the osteogenic effect induced by icariin.
authors.affiliation: Department of Clinical Pharmacy, Taizhou Hospital of Zhejiang Province, Xi Men Street No. 150, Lin Hai, Zhejiang Province 317000, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Clinical Pharmacy, Taizhou Hospital of Zhejiang Province, Xi Men Street No. 150, Lin Hai, Zhejiang Province 317000, China.
authors.forename: Zheng Li
authors.initials: ZL
authors.lastname: Jiang
authors.affiliation: Public Scientific Research Platform, Taizhou Hospital of Zhejiang Province, Xi Men Street No. 150, Lin Hai, Zhejiang Province 317000, China.
authors.forename: Li Hua
authors.initials: LH
authors.lastname: Chen
authors.affiliation: Department of Clinical Pharmacy, Taizhou Hospital of Zhejiang Province, Xi Men Street No. 150, Lin Hai, Zhejiang Province 317000, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Clinical Pharmacy, Taizhou Hospital of Zhejiang Province, Xi Men Street No. 150, Lin Hai, Zhejiang Province 317000, China.
authors.forename: Sai Zhen
authors.initials: SZ
authors.lastname: Chen
authors.affiliation: Department of Clinical Pharmacy, Taizhou Hospital of Zhejiang Province, Xi Men Street No. 150, Lin Hai, Zhejiang Province 317000, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Department of Clinical Pharmacy, Taizhou Hospital of Zhejiang Province, Xi Men Street No. 150, Lin Hai, Zhejiang Province 317000, China.
authors.forename: Ai Xiao
authors.initials: AX
authors.lastname: Xia
authors.affiliation: Department of Clinical Pharmacy, Taizhou Hospital of Zhejiang Province, Xi Men Street No. 150, Lin Hai, Zhejiang Province 317000, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Clinical Pharmacy, Taizhou Hospital of Zhejiang Province, Xi Men Street No. 150, Lin Hai, Zhejiang Province 317000, China.
authors.forename: Yan Wu
authors.initials: YW
authors.lastname: Zhu
authors.affiliation: Rehabilitation Department, Taizhou Hospital of Zhejiang Province, Xi Men Street No. 150, Lin Hai, Zhejiang Province 317000, China. Electronic address: 360081868@qq.com.
authors.forename: Dan Yang
authors.initials: DY
authors.lastname: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D016350:Leucine Zippers / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D053245:RANK Ligand / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D005419:Flavonoids; D005938:Glucocorticoids; D053245:RANK Ligand; D012333:RNA, Messenger; D014157:Transcription Factors; D003907:Dexamethasone; C056599:icariin
keywords: GILZ; Icariin; MC3T3-E1; OPG; Osteogenic; RANKL