PMID- 31749391
OWN - NLM
STAT- MEDLINE
DCOM- 20220202
LR  - 20220202
IS  - 1607-8438 (Electronic)
IS  - 0300-8207 (Linking)
VI  - 62
IP  - 2
DP  - 2021 Mar
TI  - ERK5 negatively regulates Kruppel-like factor 4 and promotes osteogenic lineage 
      cell proliferation in response to MEK5 overexpression or fluid shear stress.
PG  - 194-205
LID - 10.1080/03008207.2019.1670650 [doi]
AB  - Aim of the study: Fluid shear stress (FSS) plays a critical role in osteoblast 
      proliferation via extracellular signal-regulated kinase 5 (ERK5). Kruppel-like 
      factor 4 (KLF4) knockout robustly enhances bone formation due to increased 
      osteoblast differentiation and mineralization. However, the effect of KLF4 on 
      osteoblast proliferation is unresolved. Therefore, the aim of our study was to 
      investigate the effect of KLF4 on osteogenic lineage cell proliferation and the 
      relationship between KLF4 and ERK5. Materials and methods: MC3T3-E1 cells were 
      treated with FSS and/or KLF4 siRNA, cell viability was accessed by Edu labeling 
      and CCK-8 assay, and proliferative gene expression were assessed by PCR array. 
      Bone marrow stromal cells (BMSCs) were infected with adenovirus expressing KLF4 
      and/or constitutively active MEK5, cell viability was evaluated using crystal 
      violet staining, colony formation assay, and cell WST1 assay. The levels of KLF4 
      and ERK5 phosphorylation were identified through qRT-PCR and western blot, 
      respectively. Results: KLF4 expression was significantly down-regulated by FSS 
      exposure, however, this was reversed by ERK5 siRNA. KLF4 overexpression inhibited 
      colony formation efficiency and cell viability in BMSCs. Adenoviruses expressing 
      constitutively active MEK5 increased ERK5 phosphorylation, which inhibited KLF4 
      expression, and promoted BMSC proliferation. FSS-induced osteoblast proliferation 
      also involved elevation of Cyclin B2 and Cdc14b as well as repressed expression 
      of P27. Conclusions: KLF4 negatively regulates osteogenic lineage cell 
      proliferation, and ERK5 negatively regulates KLF4 expression and promotes 
      osteogenic lineage cell proliferation.
FAU - Zhang, Bo
AU  - Zhang B
AD  - Department of Orthopaedic Surgery or Institute of Bone and Joint Research, The 
      Second Hospital of Lanzhou University , Lanzhou, Gansu, China.
AD  - Department of Orthopaedic Surgery, Key Laboratory of Orthopedics of Gansu 
      Province , Lanzhou, Gansu, China.
FAU - An, Liping
AU  - An L
AD  - Department of Orthopaedic Surgery or Institute of Bone and Joint Research, The 
      Second Hospital of Lanzhou University , Lanzhou, Gansu, China.
AD  - Department of Orthopaedic Surgery, Key Laboratory of Orthopedics of Gansu 
      Province , Lanzhou, Gansu, China.
FAU - Geng, Bin
AU  - Geng B
AD  - Department of Orthopaedic Surgery or Institute of Bone and Joint Research, The 
      Second Hospital of Lanzhou University , Lanzhou, Gansu, China.
AD  - Department of Orthopaedic Surgery, Key Laboratory of Orthopedics of Gansu 
      Province , Lanzhou, Gansu, China.
FAU - Ding, Ning
AU  - Ding N
AD  - Department of Orthopaedic Surgery, Key Laboratory of Orthopedics of Gansu 
      Province , Lanzhou, Gansu, China.
AD  - Department of Orthopaedic Surgery, People's Hospital of Gansu Province , Lanzhou, 
      Gansu, China.
FAU - Coalson, Elam
AU  - Coalson E
AD  - Pritzker School of Medicine, University of Chicago , Chicago, IL, USA.
FAU - Wan, Lang
AU  - Wan L
AD  - Department of Orthopaedic Surgery or Institute of Bone and Joint Research, The 
      Second Hospital of Lanzhou University , Lanzhou, Gansu, China.
AD  - Department of Orthopaedic Surgery, Key Laboratory of Orthopedics of Gansu 
      Province , Lanzhou, Gansu, China.
FAU - Yan, Liang
AU  - Yan L
AD  - Department of Orthopaedic Surgery or Institute of Bone and Joint Research, The 
      Second Hospital of Lanzhou University , Lanzhou, Gansu, China.
AD  - Department of Orthopaedic Surgery, Key Laboratory of Orthopedics of Gansu 
      Province , Lanzhou, Gansu, China.
FAU - Mohammed, Fawaz H A
AU  - Mohammed FHA
AD  - Department of Orthopaedic Surgery or Institute of Bone and Joint Research, The 
      Second Hospital of Lanzhou University , Lanzhou, Gansu, China.
AD  - Department of Orthopaedic Surgery, Key Laboratory of Orthopedics of Gansu 
      Province , Lanzhou, Gansu, China.
FAU - Ma, Chongwen
AU  - Ma C
AD  - Department of Orthopaedic Surgery or Institute of Bone and Joint Research, The 
      Second Hospital of Lanzhou University , Lanzhou, Gansu, China.
AD  - Department of Orthopaedic Surgery, Key Laboratory of Orthopedics of Gansu 
      Province , Lanzhou, Gansu, China.
FAU - Li, Rui
AU  - Li R
AD  - Department of Orthopaedic Surgery or Institute of Bone and Joint Research, The 
      Second Hospital of Lanzhou University , Lanzhou, Gansu, China.
AD  - Department of Orthopaedic Surgery, Key Laboratory of Orthopedics of Gansu 
      Province , Lanzhou, Gansu, China.
FAU - Yang, Xinxin
AU  - Yang X
AD  - Department of Orthopaedic Surgery or Institute of Bone and Joint Research, The 
      Second Hospital of Lanzhou University , Lanzhou, Gansu, China.
AD  - Department of Orthopaedic Surgery, Key Laboratory of Orthopedics of Gansu 
      Province , Lanzhou, Gansu, China.
FAU - Zhang, Xiaohui
AU  - Zhang X
AD  - Department of Orthopaedic Surgery or Institute of Bone and Joint Research, The 
      Second Hospital of Lanzhou University , Lanzhou, Gansu, China.
AD  - Department of Orthopaedic Surgery, Key Laboratory of Orthopedics of Gansu 
      Province , Lanzhou, Gansu, China.
FAU - Wang, Cuifang
AU  - Wang C
AD  - Department of Orthopaedic Surgery or Institute of Bone and Joint Research, The 
      Second Hospital of Lanzhou University , Lanzhou, Gansu, China.
AD  - Department of Orthopaedic Surgery, Key Laboratory of Orthopedics of Gansu 
      Province , Lanzhou, Gansu, China.
FAU - Ma, Jinglin
AU  - Ma J
AD  - Department of Orthopaedic Surgery or Institute of Bone and Joint Research, The 
      Second Hospital of Lanzhou University , Lanzhou, Gansu, China.
AD  - Department of Orthopaedic Surgery, Key Laboratory of Orthopedics of Gansu 
      Province , Lanzhou, Gansu, China.
FAU - Xia, Yayi
AU  - Xia Y
AD  - Department of Orthopaedic Surgery or Institute of Bone and Joint Research, The 
      Second Hospital of Lanzhou University , Lanzhou, Gansu, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191121
PL  - England
TA  - Connect Tissue Res
JT  - Connective tissue research
JID - 0365263
RN  - 0 (Klf4 protein, mouse)
RN  - 0 (Kruppel-Like Factor 4)
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 7)
SB  - IM
MH  - Animals
MH  - Cell Proliferation
MH  - Kruppel-Like Factor 4
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 7/genetics
MH  - *Osteogenesis
MH  - RNA, Small Interfering
OTO - NOTNLM
OT  - Fluid shear stress
OT  - Kruppel-like factor 4
OT  - extracellular signal-regulated kinase 5
OT  - osteoblast
OT  - proliferation
EDAT- 2019/11/22 06:00
MHDA- 2022/02/03 06:00
CRDT- 2019/11/22 06:00
PHST- 2019/11/22 06:00 [pubmed]
PHST- 2022/02/03 06:00 [medline]
PHST- 2019/11/22 06:00 [entrez]
AID - 10.1080/03008207.2019.1670650 [doi]
PST - ppublish
SO  - Connect Tissue Res. 2021 Mar;62(2):194-205. doi: 10.1080/03008207.2019.1670650. 
      Epub 2019 Nov 21.