PMID- 32290615
OWN - NLM
STAT- MEDLINE
DCOM- 20201007
LR  - 20240328
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 8
DP  - 2020 Apr 12
TI  - Expression of a Constitutively Active Form of Hck in Chondrocytes Activates Wnt 
      and Hedgehog Signaling Pathways, and Induces Chondrocyte Proliferation in Mice.
LID - 10.3390/ijms21082682 [doi]
LID - 2682
AB  - Runx2 is required for chondrocyte proliferation and maturation. In the search of 
      Runx2 target genes in chondrocytes, we found that Runx2 up-regulated the 
      expression of hematopoietic cell kinase (Hck), which is a member of the Src 
      tyrosine kinase family, in chondrocytes, that Hck expression was high in 
      cartilaginous limb skeletons of wild-type mice but low in those of Runx2(-/-) 
      mice, and that Runx2 bound the promoter region of Hck. To investigate the 
      functions of Hck in chondrocytes, transgenic mice expressing a constitutively 
      active form of Hck (Hck(CA)) were generated using the Col2a1 promoter/enhancer. 
      The hind limb skeletons were fused, the tibia became a large, round mass, and the 
      growth plate was markedly disorganized. Chondrocyte maturation was delayed until 
      E16.5 but accelerated thereafter. BrdU-labeled, but not terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL)-positive, chondrocytes were 
      increased. Furthermore, Hck knock-down reduced the proliferation of primary 
      chondrocytes. In microarray and real-time RT-PCR analyses using hind limb RNA 
      from Hck(CA) transgenic mice, the expression of Wnt (Wnt10b, Tcf7, Lef1, Dkk1) 
      and hedgehog (Ihh, Ptch1, and Gli1) signaling pathway genes was upregulated. 
      These findings indicated that Hck, whose expression is regulated by Runx2, is 
      highly expressed in chondrocytes, and that Hck(CA) activates Wnt and hedgehog 
      signaling pathways, and promotes chondrocyte proliferation without increasing 
      apoptosis.
FAU - Matsuura, Viviane K S Kawata
AU  - Matsuura VKSK
AD  - Basic and Translational Research Center for Hard Tissue Disease, Nagasaki 
      University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.
FAU - Yoshida, Carolina Andrea
AU  - Yoshida CA
AD  - Basic and Translational Research Center for Hard Tissue Disease, Nagasaki 
      University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.
FAU - Komori, Hisato
AU  - Komori H
AD  - Basic and Translational Research Center for Hard Tissue Disease, Nagasaki 
      University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.
FAU - Sakane, Chiharu
AU  - Sakane C
AD  - Division of Comparative Medicine, Life Science Support Center, Nagasaki 
      University, Nagasaki 852-8523, Japan.
FAU - Yamana, Kei
AU  - Yamana K
AD  - Teijin Institute for Bio-Medical Research, TEIJIN LIMITED, Tokyo 100-8585, Japan.
FAU - Jiang, Qing
AU  - Jiang Q
AD  - Basic and Translational Research Center for Hard Tissue Disease, Nagasaki 
      University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.
FAU - Komori, Toshihisa
AU  - Komori T
AD  - Basic and Translational Research Center for Hard Tissue Disease, Nagasaki 
      University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.
LA  - eng
GR  - 18K17017/Japanese Ministry of Education, Culture, Sports, Science and Technology/
GR  - 19K18946/Japanese Ministry of Education, Culture, Sports, Science and Technology/
GR  - 18H05283/Japanese Ministry of Education, Culture, Sports, Science and Technology/
PT  - Journal Article
DEP - 20200412
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Core Binding Factor Alpha 1 Subunit)
RN  - 0 (Hedgehog Proteins)
RN  - EC 2.7.10.2 (Hck protein, mouse)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins c-hck)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - Cell Proliferation/*physiology
MH  - Cells, Cultured
MH  - Chondrocytes/*metabolism/*physiology
MH  - Core Binding Factor Alpha 1 Subunit/metabolism
MH  - Hedgehog Proteins/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Proto-Oncogene Proteins c-hck/*metabolism
MH  - Signal Transduction/*physiology
MH  - Wnt Signaling Pathway/*physiology
PMC - PMC7215647
OTO - NOTNLM
OT  - Hck
OT  - Runx2
OT  - Wnt
OT  - chondrocyte proliferation
OT  - hedgehog
COIS- The authors declare no conflict of interest.
EDAT- 2020/04/16 06:00
MHDA- 2020/10/08 06:00
PMCR- 2020/04/01
CRDT- 2020/04/16 06:00
PHST- 2020/03/11 00:00 [received]
PHST- 2020/03/30 00:00 [revised]
PHST- 2020/04/09 00:00 [accepted]
PHST- 2020/04/16 06:00 [entrez]
PHST- 2020/04/16 06:00 [pubmed]
PHST- 2020/10/08 06:00 [medline]
PHST- 2020/04/01 00:00 [pmc-release]
AID - ijms21082682 [pii]
AID - ijms-21-02682 [pii]
AID - 10.3390/ijms21082682 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Apr 12;21(8):2682. doi: 10.3390/ijms21082682.