PMID- 31981979
OWN - NLM
STAT- MEDLINE
DCOM- 20201008
LR  - 20210110
IS  - 2352-3964 (Electronic)
IS  - 2352-3964 (Linking)
VI  - 52
DP  - 2020 Feb
TI  - Foxf1 knockdown promotes BMSC osteogenesis in part by activating the 
      Wnt/beta-catenin signalling pathway and prevents ovariectomy-induced bone loss.
PG  - 102626
LID - S2352-3964(20)30001-3 [pii]
LID - 10.1016/j.ebiom.2020.102626 [doi]
LID - 102626
AB  - BACKGROUND: Forkhead box protein f1 (Foxf1) is associated with cell 
      differentiation, and may be a key player in bone homoeostasis. However, the 
      effect of Foxf1 on osteogenesis of bone marrow-derived mesenchymal stem cells 
      (BMSCs) and ovariectomy-induced bone loss, as well as its clinical implications, 
      is unknown. METHODS: By quantitative reverse transcriptase-polymerase chain 
      reaction (qRT-PCR) and western blotting, we assayed Foxf1 expression in bone 
      tissue, BMSCs, and bone marrow-derived macrophages (BMMs), derived from 
      ovariectomised (OVX) mice, and during osteogenic differentiation and osteoclast 
      differentiation. Using a loss-of-function approach (small interfering RNA 
      [siRNA]-mediated knockdown) in vitro, we examined whether Foxf1 regulates 
      osteoblast differentiation of BMSCs via the Wnt/beta-catenin signalling pathway. 
      Furthermore, we assessed the anabolic effect of Foxf1 knockdown (siFoxf1) in OVX 
      mice in vivo. We also assayed the expression of Foxf1 in bone tissue derived from 
      postmenopausal osteoporosis (PMOP) patients and its link with bone mineral 
      density (BMD). Finally, we examined the effect of Foxf1 knockdown on the 
      osteoblastic differentiation of human BMSCs. FINDINGS: Foxf1 expression was 
      significantly increased in bone extract and BMSCs from OVX mice and gradually 
      decreased during osteoblastic differentiation of BMSCs but did not differ 
      significantly in OVX mouse-derived BMMs or during osteoclast differentiation. In 
      vitro, Foxf1 knockdown markedly increased the expression of osteoblast specific 
      genes, alkaline phosphatase (ALP) activity, and mineralisation. Moreover, siFoxf1 
      activated the Wnt/beta-catenin signalling pathway. The siFoxf1-induced increase in 
      osteogenic differentiation was partly rescued by inhibitor of Wnt signalling 
      (DKK1). In OVX mice, Foxf1 siRNA significantly reduced bone loss by enhancing 
      bone formation. Foxf1 expression levels negatively correlated with reduced bone 
      mass and bone formation in bone tissue from PMOP patients. Finally, Foxf1 
      knockdown significantly promoted osteogenesis by human BMSCs. INTERPRETATION: Our 
      findings indicate that Foxf1 knockdown promotes BMSC osteogenesis and prevents 
      OVX-induced bone loss. Therefore, Foxf1 has potential as a biomarker of 
      osteogenesis and may be a therapeutic target for PMOP.
CI  - Copyright (c) 2020. Published by Elsevier B.V.
FAU - Shen, Gengyang
AU  - Shen G
AD  - Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Department of 
      Spinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese 
      Medicine, Guangzhou 510405, China; Lingnan Medical Research Center of Guangzhou 
      University of Chinese Medicine, Guangzhou 510405, China.
FAU - Ren, Hui
AU  - Ren H
AD  - Department of Spinal Surgery, The First Affiliated Hospital of Guangzhou 
      University of Chinese Medicine, Guangzhou 510405, China; Lingnan Medical Research 
      Center of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
FAU - Shang, Qi
AU  - Shang Q
AD  - Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Lingnan 
      Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou 
      510405, China.
FAU - Zhao, Wenhua
AU  - Zhao W
AD  - Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Lingnan 
      Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou 
      510405, China.
FAU - Zhang, Zhida
AU  - Zhang Z
AD  - Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Lingnan 
      Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou 
      510405, China.
FAU - Yu, Xiang
AU  - Yu X
AD  - Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Lingnan 
      Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou 
      510405, China.
FAU - Tang, Kai
AU  - Tang K
AD  - Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Lingnan 
      Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou 
      510405, China.
FAU - Tang, Jingjing
AU  - Tang J
AD  - Department of Spinal Surgery, The First Affiliated Hospital of Guangzhou 
      University of Chinese Medicine, Guangzhou 510405, China; Lingnan Medical Research 
      Center of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
FAU - Yang, Zhidong
AU  - Yang Z
AD  - Department of Spinal Surgery, The First Affiliated Hospital of Guangzhou 
      University of Chinese Medicine, Guangzhou 510405, China; Lingnan Medical Research 
      Center of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
FAU - Liang, De
AU  - Liang D
AD  - Department of Spinal Surgery, The First Affiliated Hospital of Guangzhou 
      University of Chinese Medicine, Guangzhou 510405, China; Lingnan Medical Research 
      Center of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
FAU - Jiang, Xiaobing
AU  - Jiang X
AD  - Department of Spinal Surgery, The First Affiliated Hospital of Guangzhou 
      University of Chinese Medicine, Guangzhou 510405, China; Lingnan Medical Research 
      Center of Guangzhou University of Chinese Medicine, Guangzhou 510405, China. 
      Electronic address: spinedrjxb@sina.com.
LA  - eng
PT  - Journal Article
DEP - 20200122
PL  - Netherlands
TA  - EBioMedicine
JT  - EBioMedicine
JID - 101647039
RN  - 0 (Biomarkers)
RN  - 0 (FOXF1 protein, human)
RN  - 0 (Forkhead Transcription Factors)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Biomarkers
MH  - Bone Density
MH  - Bone and Bones/diagnostic imaging/metabolism/pathology
MH  - Cell Differentiation
MH  - Cell Proliferation
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Female
MH  - Forkhead Transcription Factors/*deficiency
MH  - Gene Expression
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Immunohistochemistry
MH  - Mesenchymal Stem Cells/*cytology/*metabolism
MH  - Mice
MH  - Osteoblasts/cytology/metabolism
MH  - Osteogenesis/*genetics
MH  - Osteoporosis/diagnostic imaging/*etiology/*metabolism/pathology
MH  - Ovariectomy/*adverse effects
MH  - *Wnt Signaling Pathway
MH  - X-Ray Microtomography
MH  - Young Adult
PMC - PMC6992955
OTO - NOTNLM
OT  - Bone metabolism
OT  - Foxf1
OT  - Mesenchymal stem cells
OT  - Osteogenic differentiation
OT  - Postmenopausal osteoporosis
COIS- Declarations of Competing Interest The authors declare no competing interests.
EDAT- 2020/01/26 06:00
MHDA- 2020/10/09 06:00
PMCR- 2020/01/22
CRDT- 2020/01/26 06:00
PHST- 2019/07/24 00:00 [received]
PHST- 2019/11/22 00:00 [revised]
PHST- 2019/12/03 00:00 [accepted]
PHST- 2020/01/26 06:00 [pubmed]
PHST- 2020/10/09 06:00 [medline]
PHST- 2020/01/26 06:00 [entrez]
PHST- 2020/01/22 00:00 [pmc-release]
AID - S2352-3964(20)30001-3 [pii]
AID - 102626 [pii]
AID - 10.1016/j.ebiom.2020.102626 [doi]
PST - ppublish
SO  - EBioMedicine. 2020 Feb;52:102626. doi: 10.1016/j.ebiom.2020.102626. Epub 2020 Jan 
      22.