PMID- 28239825
OWN - NLM
STAT- MEDLINE
DCOM- 20170731
LR  - 20201209
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 21
IP  - 3
DP  - 2017 Feb
TI  - Upregulated serum sclerostin level in the T2DM patients with femur fracture 
      inhibits the expression of bone formation/remodeling-associated biomarkers via 
      antagonizing Wnt signaling.
PG  - 470-478
LID - 12152 [pii]
AB  - OBJECTIVE: Bone formation/remodeling-associated biomarkers, such as osteocalcin, 
      amino pro-peptide of type 1 collagen (P1NP) and CrossLaps (CTX) have been 
      deregulated in type 2 diabetes mellitus (T2DM) patients. In particular, the 
      T2DM-associated sclerostin markedly inhibits the bone formation, suppresses the 
      osteoblast activity and downregulates the bone turnover. PATIENTS AND METHODS: In 
      the present study, we examined the serum levels of sclerostin, osteocalcin, P1NP 
      and CTX in the T2DM patients. We evaluated the regulation on osteocalcin, P1NP 
      and CTX by sclerostin treatment in osteoblast hFOB 1.19 cells. Finally, we 
      determined the mediation of Wnt signaling in the regulation by sclerostin on 
      osteocalcin, P1NP and CTX in human osteoblast hFOB 1.19 cells. RESULTS: It was 
      demonstrated that osteocalcin, P1NP and CTX were downregulated in the femur 
      fracture of patients with T2DM, whereas the serum level of the sclerostin was 
      markedly higher in the femur fracture of patients with T2DM. Moreover, the 
      downregulated osteocalcin, P1NP or CTX was negatively associated with the 
      upregulated sclerostin. In vitro results confirmed that sclerostin downregulated 
      the expression of osteocalcin, P1NP and CTX in hFOB 1.19 cells. Also, our results 
      demonstrated that Wnt/beta-catenin inhibition was associated with the 
      sclerostin-mediated inhibition of osteocalcin, P1NP and CTX in hFOB 1.19 cells. 
      The Wnt/beta-catenin level was markedly inhibited by sclerostin treatment, and the 
      siRNA-mediated downregulation of beta-catenin reduced the levels of osteocalcin, 
      P1NP and CTX. CONCLUSIONS: Our study demonstrated that the upregulated serum 
      sclerostin level in the T2DM patients with fracture inhibited the expression of 
      the bone formation/remodeling-associated biomarkers via antagonizing Wnt 
      signaling. It suggests that sclerostin might be an effective target for 
      T2DM-associated bone fracture and delayed fracture healing.
FAU - Wu, Y
AU  - Wu Y
AD  - Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical 
      University, Guangzhou, China. guoxinnifj@sina.com.
FAU - Xu, S-Y
AU  - Xu SY
FAU - Liu, S-Y
AU  - Liu SY
FAU - Xu, L
AU  - Xu L
FAU - Deng, S-Y
AU  - Deng SY
FAU - He, Y-B
AU  - He YB
FAU - Xian, S-C
AU  - Xian SC
FAU - Liu, Y-H
AU  - Liu YH
FAU - Ni, G-X
AU  - Ni GX
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Biomarkers)
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Genetic Markers)
RN  - 0 (Peptide Fragments)
RN  - 0 (Procollagen)
RN  - 0 (SOST protein, human)
RN  - 0 (Wnt Proteins)
RN  - 0 (beta Catenin)
RN  - 0 (glutamyl-lysyl-alanyl-histidyl-aspartyl-glycyl-glycyl-arginine)
RN  - 0 (procollagen Type I N-terminal peptide)
RN  - 104982-03-8 (Osteocalcin)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Adult
MH  - Biomarkers/blood
MH  - Bone Morphogenetic Proteins/*blood
MH  - *Bone Remodeling
MH  - Cell Line
MH  - Collagen/blood
MH  - Diabetes Mellitus, Type 2/*blood/complications
MH  - Female
MH  - Femur/pathology
MH  - Fractures, Bone/*blood
MH  - Genetic Markers
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Osteocalcin/blood
MH  - *Osteogenesis
MH  - Peptide Fragments/blood
MH  - Procollagen/blood
MH  - Wnt Proteins/metabolism
MH  - *Wnt Signaling Pathway
MH  - beta Catenin/metabolism
EDAT- 2017/02/28 06:00
MHDA- 2017/08/02 06:00
CRDT- 2017/02/28 06:00
PHST- 2017/02/28 06:00 [entrez]
PHST- 2017/02/28 06:00 [pubmed]
PHST- 2017/08/02 06:00 [medline]
AID - 12152 [pii]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2017 Feb;21(3):470-478.