PMID- 28560408
OWN - NLM
STAT- MEDLINE
DCOM- 20180316
LR  - 20181113
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 40
IP  - 1
DP  - 2017 Jul
TI  - Collagen-derived N-acetylated proline-glycine-proline upregulates the expression 
      of pro-inflammatory cytokines and extracellular matrix proteases in nucleus 
      pulposus cells via the NF-kappaB and MAPK signaling pathways.
PG  - 164-174
LID - 10.3892/ijmm.2017.3005 [doi]
AB  - N-acetylated proline-glycine-proline (N-Ac-PGP) is a chemokine involved in 
      inflammatory diseases and is found to accumulate in degenerative discs. N-Ac-PGP 
      has been demonstrated to have a pro-inflammatory effect on human cartilage 
      endplate stem cells. However, the effect of N-Ac-PGP on human intervertebral disc 
      cells, especially nucleus pulposus (NP) cells, remains unknown. The purpose of 
      this study was to investigate the effect of N-Ac-PGP on the expression of 
      pro-inflammatory factors and extracellular matrix (ECM) proteases in NP cells and 
      the molecular mechanism underlying this effect. Therefore, Milliplex assays were 
      used to detect the levels of various inflammatory cytokines in conditioned 
      culture medium of NP cells treated with N-Ac-PGP, including 
      interleukin-1beta (IL-1beta), IL-6, IL-17, tumor necrosis factor-alpha (TNF-alpha) and C-C 
      motif ligand 2 (CCL2). RT-qPCR was also used to determine the expression of 
      pro-inflammatory cytokines and ECM proteases in the NP cells treated with 
      N-Ac-PGP. Moreover, the role of nuclear factor-kappaB (NF-kappaB) and mitogen-activated 
      protein kinase (MAPK) signaling pathways in mediating the effect of N-Ac-PGP on 
      the phenotype of NP cells was investigated using specific signaling inhibitors. 
      Milliplex assays showed that NP cells treated with N-Ac-PGP (10 and 100 microg/ml) 
      secreted higher levels of IL-1beta, IL-6, IL-17, TNF-alpha and CCL2 compared with the 
      control. RT-qPCR assays showed that NP cells treated with N-Ac-PGP (100 microg/ml) 
      had markedly upregulated expression of matrix metalloproteinase 3 (MMP3), MMP13, 
      a disintegrin and metalloproteinase with thrombospondin motif 4 (ADAMTS4), 
      ADAMTS5, IL-6, CCL-2, CCL-5 and C-X-C motif chemokine ligand 10 (CXCL10). 
      Moreover, N-Ac-PGP was shown to activate the MAPK and NF-kappaB signaling pathways in 
      NP cells. MAPK and NF-kappaB signaling inhibitors suppressed the upregulation of 
      proteases and pro-inflammatory cytokines in NP cells treated with N-Ac-PGP. 
      In conclusion, N-Ac-PGP induces the expression of pro-inflammatory cytokines and 
      matrix catabolic enzymes in NP cells via the NF-kappaB and MAPK signaling pathways. 
      N-Ac-PGP is a novel therapeutic target for intervertebral disc degeneration.
FAU - Feng, Chencheng
AU  - Feng C
AD  - Department of Orthopaedics, Xinqiao Hospital, The Third Military Medical 
      University, Chongqing 400037, P.R. China.
FAU - He, Jinyue
AU  - He J
AD  - Department of Orthopaedics, Xinqiao Hospital, The Third Military Medical 
      University, Chongqing 400037, P.R. China.
FAU - Zhang, Yang
AU  - Zhang Y
AD  - Department of Orthopaedics, Xinqiao Hospital, The Third Military Medical 
      University, Chongqing 400037, P.R. China.
FAU - Lan, Minghong
AU  - Lan M
AD  - Department of Orthopaedics, Xinqiao Hospital, The Third Military Medical 
      University, Chongqing 400037, P.R. China.
FAU - Yang, Minghui
AU  - Yang M
AD  - Department of Orthopaedics, Xinqiao Hospital, The Third Military Medical 
      University, Chongqing 400037, P.R. China.
FAU - Liu, Huan
AU  - Liu H
AD  - Department of Orthopaedics, Xinqiao Hospital, The Third Military Medical 
      University, Chongqing 400037, P.R. China.
FAU - Huang, Bo
AU  - Huang B
AD  - Department of Orthopaedics, Xinqiao Hospital, The Third Military Medical 
      University, Chongqing 400037, P.R. China.
FAU - Pan, Yong
AU  - Pan Y
AD  - Department of Orthopaedics, Xinqiao Hospital, The Third Military Medical 
      University, Chongqing 400037, P.R. China.
FAU - Zhou, Yue
AU  - Zhou Y
AD  - Department of Orthopaedics, Xinqiao Hospital, The Third Military Medical 
      University, Chongqing 400037, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20170529
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Cytokines)
RN  - 0 (NF-kappa B)
RN  - 0 (Oligopeptides)
RN  - 9007-34-5 (Collagen)
RN  - EC 3.4.24.- (Collagenases)
SB  - IM
MH  - Adult
MH  - Cell Line
MH  - Collagen/*chemistry
MH  - Collagenases/*biosynthesis
MH  - Cytokines/*biosynthesis
MH  - Female
MH  - Humans
MH  - Intervertebral Disc/*metabolism/pathology
MH  - Intervertebral Disc Degeneration/metabolism/pathology
MH  - MAP Kinase Signaling System/*drug effects
MH  - Male
MH  - Middle Aged
MH  - NF-kappa B/*metabolism
MH  - Oligopeptides/chemistry/*pharmacology
MH  - Up-Regulation/*drug effects
PMC - PMC5466390
EDAT- 2017/06/01 06:00
MHDA- 2018/03/17 06:00
PMCR- 2017/05/29
CRDT- 2017/06/01 06:00
PHST- 2016/12/13 00:00 [received]
PHST- 2017/05/18 00:00 [accepted]
PHST- 2017/06/01 06:00 [pubmed]
PHST- 2018/03/17 06:00 [medline]
PHST- 2017/06/01 06:00 [entrez]
PHST- 2017/05/29 00:00 [pmc-release]
AID - ijmm-40-01-0164 [pii]
AID - 10.3892/ijmm.2017.3005 [doi]
PST - ppublish
SO  - Int J Mol Med. 2017 Jul;40(1):164-174. doi: 10.3892/ijmm.2017.3005. Epub 2017 May 
      29.