PMID- 29260521
OWN - NLM
STAT- MEDLINE
DCOM- 20181025
LR  - 20181025
IS  - 1672-173X (Print)
IS  - 1672-173X (Linking)
VI  - 48
IP  - 6
DP  - 2017 Nov
TI  - [Research on Relationship of HIF-1 Signaling Pathway and Postmenstrual 
      Osteoporosis].
PG  - 862-868
AB  - OBJECTIVE: Exploring the role of hypoxia-induceibal factor-1 (HIF-1) signaling 
      pathway in postmenstrual osteoporosis (PMOP) and how to play a role in PMOP. 
      METHODS: Sixty C57BL/6J female mouse were randomly divided into 4 groups: 
      sham-operation group (A group),ovariectomized PMOP group (B group),HIF-1 alpha 
      inhibitor 2-methoxy estradiol (2ME2) treatment group(D group) and solvent control 
      group(C group),15 mice in each group. There months after modeling,the metabolism 
      product of mouse bone tissue including serum propeptide of typeⅠ procollagen 
      (PINP),C-terminal telopeptide-Ⅰ (CTX-1) and serum estrogen were quantified by 
      enzyme-linked immunosorbent assay (ELISA). Changes of bone structure were 
      observed on HE stained tissue sections. Regulation products of HIF-1 signaling 
      pathway including HIF-1alpha,HIF-1beta,specific prolyl hydroxylases (PHD),Hipple-Lindau 
      tumor suppressor protein (VHL),and factor inhibiting HIF (FIH) were measured by 
      immuno-histochenmistry staining. Osteoclasts derived from OVX-mice were treated 
      with inhibitors of extracellular regulated protein kinases (ERK),protein kinase B 
      (Akt) and nuclear factor kappa B (NF-kappaB) signaling pathways. HIF-1alpha expression 
      were detected by Western blot to obtain a rudimentary knowledge of possible 
      mechanism of up-regulation of HIF-1alpha in osteoclasts of postmenospausal 
      osteoporosis. RESULTS: Metabolism product of mouse bone tissue of B group were 
      higher than A group ( P<0.001). The positive expression of HIF-1-alpha protein 
      was found in osteoclasts,and the expression of HIF-1-alpha protein in bone marrow 
      region was higher than that in A group ( P<0.001), while the change od 
      HIF-1beta,PHD,VHL,and FIH were not obviously. After the HIF-1alpha inhibitor 
      treatment,markers of bone resorption of bone metabolism in ovariectomized mice 
      reduced and the osteoporosis get greatly relieved ( P<0.001). HIF-1alpha expression 
      was down-regulated in osteoclasts of OVX-mice after treated with inhibitors of 
      ERK,Akt and NF-kappaB signaling pathways ( P<0.05). CONCLUSION: HIF-1 signaling 
      pathway get involved in the pathological evolution of osteoporosis after 
      menopause,and inhibition of HIF-1 can significantly improve the severity of 
      osteoporosis after menopause. ERK,Akt and NF-kappaB signaling pathways may involve in 
      the up-regulation of HIF-1 signaling pathway in osteoclasts of PMOP.
FAU - Zhong, Hang
AU  - Zhong H
AD  - Department of Orthopedic Surgery,West China Hospital, Sichuan University,Chengdu 
      610041,China.
FAU - Cao, Can
AU  - Cao C
AD  - Department of Orthopedic Surgery,Hebei General Hospital,Shijiazhuang 
      050051,China.
FAU - Yang, Jing
AU  - Yang J
AD  - Department of Orthopedic Surgery,West China Hospital, Sichuan University,Chengdu 
      610041,China.
FAU - Huang, Qiang
AU  - Huang Q
AD  - Department of Orthopedic Surgery,West China Hospital, Sichuan University,Chengdu 
      610041,China.
LA  - chi
PT  - Journal Article
PL  - China
TA  - Sichuan Da Xue Xue Bao Yi Xue Ban
JT  - Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical 
      science edition
JID - 101162609
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (NF-kappa B)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Female
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - MAP Kinase Signaling System
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/metabolism
MH  - Osteoclasts/*metabolism
MH  - Osteoporosis/*metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - *Signal Transduction
OTO - NOTNLM
OT  - HIF-1alpha
OT  - Osteoclast
OT  - Osteoporosis
OT  - Ovariectomy
EDAT- 2017/12/21 06:00
MHDA- 2018/10/26 06:00
CRDT- 2017/12/21 06:00
PHST- 2017/12/21 06:00 [entrez]
PHST- 2017/12/21 06:00 [pubmed]
PHST- 2018/10/26 06:00 [medline]
PST - ppublish
SO  - Sichuan Da Xue Xue Bao Yi Xue Ban. 2017 Nov;48(6):862-868.