PMID- 28883757
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1226-4512 (Print)
IS  - 2093-3827 (Electronic)
IS  - 1226-4512 (Linking)
VI  - 21
IP  - 5
DP  - 2017 Sep
TI  - Time-dependent proteomic and genomic alterations in Toll-like 
      receptor-4-activated human chondrocytes: increased expression of lamin A/C and 
      annexins.
PG  - 531-546
LID - 10.4196/kjpp.2017.21.5.531 [doi]
AB  - Activation of Toll-like receptor-4 (TLR-4) in articular chondrocytes increases 
      the catabolic compartment and leads to matrix degradation during the development 
      of osteoarthritis. In this study, we determined the proteomic and genomic 
      alterations in human chondrocytes during lipopolysaccharide (LPS)-induced 
      inflammation to elucidate the underlying mechanisms and consequences of TLR-4 
      activation. Human chondrocytes were cultured with LPS for 12, 24, and 36 h to 
      induce TLR-4 activation. The TLR-4-induced inflammatory response was confirmed by 
      real-time PCR analysis of increased interleukin-1 beta (IL-1beta), interleukin-6 
      (IL-6), and tumor necrosis factor alpha (TNF-alpha) expression levels. In 
      TLR-4-activated chondrocytes, proteomic changes were determined by 
      two-dimensional electrophoresis and matrix-assisted laser 
      desorption/ionization-mass spectroscopy analysis, and genomic changes were 
      determined by microarray and gene ontology analyses. Proteomics analysis 
      identified 26 proteins with significantly altered expression levels; these 
      proteins were related to the cytoskeleton and oxidative stress responses. Gene 
      ontology analysis indicated that LPS treatment altered specific functional 
      pathways including 'chemotaxis', 'hematopoietic organ development', 'positive 
      regulation of cell proliferation', and 'regulation of cytokine biosynthetic 
      process'. Nine of the 26 identified proteins displayed the same increased 
      expression patterns in both proteomics and genomics analyses. Western blot 
      analysis confirmed the LPS-induced increases in expression levels of lamin A/C 
      and annexins 4/5/6. In conclusion, this study identified the time-dependent 
      genomic, proteomic, and functional pathway alterations that occur in chondrocytes 
      during LPS-induced TLR-4 activation. These results provide valuable new insights 
      into the underlying mechanisms that control the development and progression of 
      osteoarthritis.
FAU - Ha, Seung Hee
AU  - Ha SH
AD  - National Research Laboratory for Mitochondrial Signaling, Department of 
      Physiology, Department of Health Sciences and Technology, BK21 Plus Project Team, 
      College of Medicine, Cardiovascular and Metabolic Disease Center, Inje 
      University, Busan 47392, Korea.
AD  - Department of Health Technology Development, Health Project Management Team, 
      Korea Health Industry Development Institute (KHIDI), Cheongju 28159, Korea.
FAU - Kim, Hyoung Kyu
AU  - Kim HK
AD  - National Research Laboratory for Mitochondrial Signaling, Department of 
      Physiology, Department of Health Sciences and Technology, BK21 Plus Project Team, 
      College of Medicine, Cardiovascular and Metabolic Disease Center, Inje 
      University, Busan 47392, Korea.
FAU - Anh, Nguyen Thi Tuyet
AU  - Anh NTT
AD  - National Research Laboratory for Mitochondrial Signaling, Department of 
      Physiology, Department of Health Sciences and Technology, BK21 Plus Project Team, 
      College of Medicine, Cardiovascular and Metabolic Disease Center, Inje 
      University, Busan 47392, Korea.
FAU - Kim, Nari
AU  - Kim N
AD  - National Research Laboratory for Mitochondrial Signaling, Department of 
      Physiology, Department of Health Sciences and Technology, BK21 Plus Project Team, 
      College of Medicine, Cardiovascular and Metabolic Disease Center, Inje 
      University, Busan 47392, Korea.
FAU - Ko, Kyung Soo
AU  - Ko KS
AD  - National Research Laboratory for Mitochondrial Signaling, Department of 
      Physiology, Department of Health Sciences and Technology, BK21 Plus Project Team, 
      College of Medicine, Cardiovascular and Metabolic Disease Center, Inje 
      University, Busan 47392, Korea.
FAU - Rhee, Byoung Doo
AU  - Rhee BD
AD  - National Research Laboratory for Mitochondrial Signaling, Department of 
      Physiology, Department of Health Sciences and Technology, BK21 Plus Project Team, 
      College of Medicine, Cardiovascular and Metabolic Disease Center, Inje 
      University, Busan 47392, Korea.
FAU - Han, Jin
AU  - Han J
AD  - National Research Laboratory for Mitochondrial Signaling, Department of 
      Physiology, Department of Health Sciences and Technology, BK21 Plus Project Team, 
      College of Medicine, Cardiovascular and Metabolic Disease Center, Inje 
      University, Busan 47392, Korea.
LA  - eng
PT  - Journal Article
DEP - 20170822
PL  - Korea (South)
TA  - Korean J Physiol Pharmacol
JT  - The Korean journal of physiology & pharmacology : official journal of the Korean 
      Physiological Society and the Korean Society of Pharmacology
JID - 9709505
PMC - PMC5587603
OTO - NOTNLM
OT  - Annexin 4/5/6
OT  - Chondrocyte
OT  - Lamin A/C
OT  - Omics
OT  - Toll-like receptor-4
COIS- CONFLICTS OF INTEREST: The authors declare no conflicts of interest.
EDAT- 2017/09/09 06:00
MHDA- 2017/09/09 06:01
PMCR- 2017/09/01
CRDT- 2017/09/09 06:00
PHST- 2017/04/10 00:00 [received]
PHST- 2017/05/04 00:00 [revised]
PHST- 2017/05/10 00:00 [accepted]
PHST- 2017/09/09 06:00 [entrez]
PHST- 2017/09/09 06:00 [pubmed]
PHST- 2017/09/09 06:01 [medline]
PHST- 2017/09/01 00:00 [pmc-release]
AID - 10.4196/kjpp.2017.21.5.531 [doi]
PST - ppublish
SO  - Korean J Physiol Pharmacol. 2017 Sep;21(5):531-546. doi: 
      10.4196/kjpp.2017.21.5.531. Epub 2017 Aug 22.