PMID- 30452909
OWN - NLM
STAT- MEDLINE
DCOM- 20190501
LR  - 20190501
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 844
DP  - 2019 Feb 5
TI  - Vildagliptin reduced extracellular matrix degradation in human primary 
      chondrocytes.
PG  - 49-55
LID - S0014-2999(18)30675-7 [pii]
LID - 10.1016/j.ejphar.2018.11.020 [doi]
AB  - In the present study, we investigated the effects of the specific DPP-4 inhibitor 
      vildagliptin on degradation of type II collagen and aggrecan, the main components 
      of the articular extracellular matrix, in primary human chondrocytes. The results 
      of our study reveal that vildagliptin reduced degradation of the articular 
      extracellular matrix (ECM) by downregulating IL-1beta-induced expression of matrix 
      metalloproteinases-3 (MMP-3), matrix metalloproteinases-13 (MMP-13), a 
      disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and a 
      disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5). We 
      also found that vildagliptin ameliorated IL-1beta-induced activation of the JNK/AP-1 
      and nuclear factor-kappaB (NF-kappaB) pro-inflammatory signaling pathways by 
      downregulating phosphorylation of JNK and nuclear factor of kappa light 
      polypeptide gene enhancer in B-cells inhibitor alpha (IkappaBalpha), activation of 
      c-Fos/c-Jun, and nuclear translocation of p65. Our findings suggest that 
      vildagliptin may serve as a novel treatment for excessive degradation of the 
      articular ECM in osteoarthritis (OA).
CI  - Copyright (c) 2018. Published by Elsevier B.V.
FAU - Wang, Zhirong
AU  - Wang Z
AD  - Department of Orthopedics, Zhangjiagang Hospital of Traditional Chinese Medicine, 
      China.
FAU - Xu, Menglei
AU  - Xu M
AD  - Orthopedics and Sports Medicine Center, Suzhou Municipal Hospital (North 
      District), Nanjing Medical University Affiliated Suzhou Hospital, 242, Guangji 
      Road, Suzhou 215006, China.
FAU - Bai, Jiaxiang
AU  - Bai J
AD  - Department of Orthopedics, The First Affiliated Hospital of Soochow University, 
      188, shizi Road, Suzhou 215006, China.
FAU - Ge, Gaoran
AU  - Ge G
AD  - Department of Orthopedics, The First Affiliated Hospital of Soochow University, 
      188, shizi Road, Suzhou 215006, China.
FAU - Guo, Xiaobin
AU  - Guo X
AD  - Department of Orthopedics, The First Affiliated Hospital of Soochow University, 
      188, shizi Road, Suzhou 215006, China.
FAU - Yu, Binqing
AU  - Yu B
AD  - Department of Orthopedics, The First Affiliated Hospital of Soochow University, 
      188, shizi Road, Suzhou 215006, China.
FAU - Xiao, Long
AU  - Xiao L
AD  - Department of Orthopedics, Zhangjiagang Hospital of Traditional Chinese Medicine, 
      China.
FAU - Geng, Dechun
AU  - Geng D
AD  - Department of Orthopedics, The First Affiliated Hospital of Soochow University, 
      188, shizi Road, Suzhou 215006, China. Electronic address: szgengdc@163.com.
FAU - Hao, Yuefeng
AU  - Hao Y
AD  - Orthopedics and Sports Medicine Center, Suzhou Municipal Hospital (North 
      District), Nanjing Medical University Affiliated Suzhou Hospital, 242, Guangji 
      Road, Suzhou 215006, China. Electronic address: haoyf6708@yeah.net.
LA  - eng
PT  - Journal Article
DEP - 20181116
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Aggrecans)
RN  - 0 (Collagen Type II)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Interleukin-1beta)
RN  - EC 3.4.24.- (ADAMTS5 Protein)
RN  - EC 3.4.24.- (ADAMTS5 protein, human)
RN  - EC 3.4.24.- (MMP13 protein, human)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.82 (ADAMTS4 Protein)
RN  - EC 3.4.24.82 (ADAMTS4 protein, human)
RN  - I6B4B2U96P (Vildagliptin)
SB  - IM
MH  - ADAMTS4 Protein/genetics/metabolism
MH  - ADAMTS5 Protein/genetics/metabolism
MH  - Aggrecans/metabolism
MH  - Cells, Cultured
MH  - Chondrocytes/*drug effects
MH  - Collagen Type II/metabolism
MH  - Extracellular Matrix/*drug effects/metabolism
MH  - Humans
MH  - Hypoglycemic Agents/*pharmacology
MH  - Interleukin-1beta/pharmacology
MH  - Matrix Metalloproteinase 13/genetics/metabolism
MH  - Matrix Metalloproteinase 3/genetics/metabolism
MH  - Vildagliptin/*pharmacology
OTO - NOTNLM
OT  - ADAMTS
OT  - Aggrecan
OT  - MMPs
OT  - Osteoarthritis
OT  - Type II collagen
OT  - Vildagliptin
EDAT- 2018/11/20 06:00
MHDA- 2019/05/02 06:00
CRDT- 2018/11/20 06:00
PHST- 2018/07/24 00:00 [received]
PHST- 2018/11/12 00:00 [revised]
PHST- 2018/11/14 00:00 [accepted]
PHST- 2018/11/20 06:00 [pubmed]
PHST- 2019/05/02 06:00 [medline]
PHST- 2018/11/20 06:00 [entrez]
AID - S0014-2999(18)30675-7 [pii]
AID - 10.1016/j.ejphar.2018.11.020 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2019 Feb 5;844:49-55. doi: 10.1016/j.ejphar.2018.11.020. Epub 
      2018 Nov 16.