PMID- 25673773
OWN - NLM
STAT- MEDLINE
DCOM- 20160318
LR  - 20200930
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Linking)
VI  - 308
IP  - 9
DP  - 2015 May 1
TI  - Suppression of discoidin domain receptor 1 expression enhances the chondrogenesis 
      of adipose-derived stem cells.
PG  - C685-96
LID - 10.1152/ajpcell.00398.2014 [doi]
AB  - Effectively directing the chondrogenesis of adipose-derived stem cells (ADSCs) to 
      engineer articular cartilage represents an important challenge in ADSC-based 
      articular cartilage tissue engineering. The discoidin domain receptor 1 (DDR1) 
      has been shown to affect cartilage homeostasis; however, little is known about 
      the roles of DDR1 in ADSC chondrogenesis. In this study, we used the 
      three-dimensional culture pellet culture model system with chondrogenic induction 
      to investigate the roles of DDR1 in the chondrogenic differentiation of human 
      ADSCs (hADSCs). Real-time polymerase chain reaction and Western blot were used to 
      detect the expression of DDRs and chondrogenic genes. Sulfated glycosaminoglycan 
      (sGAG) was detected by Alcian blue and dimethylmethylene blue (DMMB) assays. 
      Terminal deoxy-nucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) 
      staining was used to assess cell death. During the chondrogenesis of hADSCs, the 
      expression of DDR1 but not DDR2 was significantly elevated. The depletion of DDR1 
      expression in hADSCs using short hairpin RNA increased the expression of 
      chondrogenic genes (SOX-9, collagen type II, and aggrecan) and cartilaginous 
      matrix deposition (collagen type II and sGAG) and only slightly increased cell 
      death (2-8%). DDR1 overexpression in hADSCs decreased the expression of 
      chondrogenic genes (SOX-9, collagen type II, and aggrecan) and sGAG and enhanced 
      hADSC survival. Moreover, DDR1-depleted hADSCs showed decreased expression of the 
      terminal differentiation genes runt-related transcription factor 2 (Runx2) and 
      matrix metalloproteinase 13 (MMP-13). These results suggest that DDR1 suppression 
      may enhance ADSC chondrogenesis by enhancing the expression of chondrogenic genes 
      and cartilaginous matrix deposition. We proposed that the suppression of DDR1 in 
      ADSCs may be a candidate strategy of genetic modification to optimize ADSC-based 
      articular cartilage tissue engineering.
CI  - Copyright (c) 2015 the American Physiological Society.
FAU - Wu, Shun-Cheng
AU  - Wu SC
AD  - Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical 
      University, Kaohsiung, Taiwan; Department of Physiology, College of Medicine, 
      Kaohsiung Medical University, Kaohsiung, Taiwan; Orthopaedic Research Center, 
      College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;
FAU - Hsiao, Hsu-Feng
AU  - Hsiao HF
AD  - Department of Family Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan;
FAU - Ho, Mei-Ling
AU  - Ho ML
AD  - Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical 
      University, Kaohsiung, Taiwan; Department of Physiology, College of Medicine, 
      Kaohsiung Medical University, Kaohsiung, Taiwan; Orthopaedic Research Center, 
      College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;
FAU - Hung, Yung-Li
AU  - Hung YL
AD  - Department of Physiology, College of Medicine, Kaohsiung Medical University, 
      Kaohsiung, Taiwan;
FAU - Chang, Je-Ken
AU  - Chang JK
AD  - Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, 
      Kaohsiung, Taiwan; Department of Orthopedics, Kaohsiung Medical University 
      Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of 
      Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung, 
      Taiwan; Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, 
      Kaohsiung Medical University, Kaohsiung, Taiwan;
FAU - Wang, Gwo-Jaw
AU  - Wang GJ
AD  - Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, 
      Kaohsiung, Taiwan; Department of Orthopedic Surgery, University of Virginia, 
      Charlottesville, Virginia; Medical Device Innovation Center, National Cheng-Kung 
      University, Tainan, Taiwan; and Skeleton-Joint Research Center, National 
      Cheng-Kung University, Tainan, Taiwan.
FAU - Wang, Chau-Zen
AU  - Wang CZ
AD  - Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical 
      University, Kaohsiung, Taiwan; Department of Physiology, College of Medicine, 
      Kaohsiung Medical University, Kaohsiung, Taiwan; Orthopaedic Research Center, 
      College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 
      czwang@kmu.edu.tw.
LA  - eng
PT  - Journal Article
DEP - 20150211
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (ACAN protein, human)
RN  - 0 (Aggrecans)
RN  - 0 (Collagen Type II)
RN  - 0 (Core Binding Factor Alpha 1 Subunit)
RN  - 0 (Glycosaminoglycans)
RN  - 0 (RNA, Messenger)
RN  - 0 (RUNX2 protein, human)
RN  - 0 (SOX9 Transcription Factor)
RN  - 0 (SOX9 protein, human)
RN  - EC 2.7.10.1 (DDR1 protein, human)
RN  - EC 2.7.10.1 (Discoidin Domain Receptor 1)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 3.4.24.- (MMP13 protein, human)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
SB  - IM
MH  - Aggrecans/genetics/metabolism
MH  - Cell Differentiation
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Chondrocytes/*metabolism
MH  - *Chondrogenesis
MH  - Collagen Type II/genetics/metabolism
MH  - Core Binding Factor Alpha 1 Subunit/genetics/metabolism
MH  - Discoidin Domain Receptor 1
MH  - Gene Expression Regulation
MH  - Glycosaminoglycans/metabolism
MH  - Humans
MH  - Matrix Metalloproteinase 13/genetics/metabolism
MH  - Phenotype
MH  - RNA Interference
MH  - RNA, Messenger/metabolism
MH  - Receptor Protein-Tyrosine Kinases/genetics/*metabolism
MH  - SOX9 Transcription Factor/genetics/metabolism
MH  - Signal Transduction
MH  - Stem Cells/*metabolism
MH  - Subcutaneous Fat/cytology/*metabolism
MH  - Time Factors
MH  - Transfection
OTO - NOTNLM
OT  - ADSCs
OT  - DDR1
OT  - adipose-derived stem cells
OT  - articular cartilage tissue engineering
OT  - chondrogenesis
OT  - discoidin domain receptor 1
EDAT- 2015/02/13 06:00
MHDA- 2016/03/19 06:00
CRDT- 2015/02/13 06:00
PHST- 2014/12/15 00:00 [received]
PHST- 2015/02/03 00:00 [accepted]
PHST- 2015/02/13 06:00 [entrez]
PHST- 2015/02/13 06:00 [pubmed]
PHST- 2016/03/19 06:00 [medline]
AID - ajpcell.00398.2014 [pii]
AID - 10.1152/ajpcell.00398.2014 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2015 May 1;308(9):C685-96. doi: 
      10.1152/ajpcell.00398.2014. Epub 2015 Feb 11.