PMID- 30600473
OWN - NLM
STAT- MEDLINE
DCOM- 20191127
LR  - 20220720
IS  - 1568-5608 (Electronic)
IS  - 0925-4692 (Linking)
VI  - 27
IP  - 5
DP  - 2019 Oct
TI  - Anti-inflammatory role of TPCA-1 encapsulated nanosomes in porcine chondrocytes 
      against TNF-alpha stimulation.
PG  - 1011-1019
LID - 10.1007/s10787-018-0542-5 [doi]
AB  - In this study, we evaluated the hypothesis that immunonanosomes carrying the drug 
      [5-(p-Fluorophenyl)-2-ureido]thiophene-3-carboxamide (TPCA-1) will help in 
      reducing nuclear factor-kappaB (NF-kappaB)-associated inflammation in porcine 
      chondrocytes against tumor necrosis factor-alpha (TNF-alpha)-induced stress. The 
      nanosomes were tagged with monoclonal anti-type II collagen (MabCII) antibody to 
      specifically target the exposed type II collagen in cartilage matrix. TPCA-1 at a 
      concentration of 10 microM significantly reduced expression of the matrix-degrading 
      enzyme, Matrix metalloproteinase-13 (MMP-13) and blocked the p65 nuclear 
      translocation. In comparison to the TPCA-1 solution alone, the TPCA-1 nanosomes 
      were found to be more effective in reducing the cellular toxicity, oxidative 
      stress and inflammation in chondrocytes treated with TNF-alpha. In addition, TPCA-1 
      nanosomes were more effective in reducing the gene expression of 
      hypoxia-inducible factor-2alpha (HIF-2alpha) that in turn is associated with the 
      regulation of MMP-13 gene. TPCA-1 nanosomes significantly reduced expression of 
      both these genes. The data also showed that TPCA-1 did not attenuate the 
      down-regulated gene expression levels of anabolic genes aggrecan (ACAN) and 
      collagen type II alpha (COL2A1). In conclusion, this study showed that TPCA-1 
      nanosomes carrying a dose of 10 microM TPCA-1 can effectively increase the survival 
      of cultured porcine chondrocytes against TNF-alpha-induced stress. The findings of 
      this study could be used to develop nanosome-based drug delivery systems (DDSs) 
      for animal model of OA. Moreover, the approach presented here can be further 
      utilized in other studies for targeted delivery of the drug of interest at a 
      cellular level.
FAU - Bhatti, Fazal Ur Rehman
AU  - Bhatti FUR
AD  - Department of Orthopaedic Surgery and Biomedical Engineering, University of 
      Tennessee Health Science Center, Research 151, VAMC, 1030 Jefferson Ave, Memphis, 
      TN, 38104, USA.
AD  - VA Medical Center, Memphis, TN, USA.
FAU - Hasty, Karen A
AU  - Hasty KA
AD  - Department of Orthopaedic Surgery and Biomedical Engineering, University of 
      Tennessee Health Science Center, Research 151, VAMC, 1030 Jefferson Ave, Memphis, 
      TN, 38104, USA. khasty@uthsc.edu.
AD  - Department of Orthopaedic Surgery and Biomedical Engineering, University of 
      Tennessee Health Science Center-Campbell Clinic, Research 151, VAMC, 1030 
      Jefferson Ave, Memphis, TN, 38104, USA. khasty@uthsc.edu.
AD  - VA Medical Center, Memphis, TN, USA. khasty@uthsc.edu.
FAU - Cho, Hongsik
AU  - Cho H
AUID- ORCID: 0000-0001-7972-5079
AD  - Department of Orthopaedic Surgery and Biomedical Engineering, University of 
      Tennessee Health Science Center, Research 151, VAMC, 1030 Jefferson Ave, Memphis, 
      TN, 38104, USA. hcho4@uthsc.edu.
AD  - Department of Orthopaedic Surgery and Biomedical Engineering, University of 
      Tennessee Health Science Center-Campbell Clinic, Research 151, VAMC, 1030 
      Jefferson Ave, Memphis, TN, 38104, USA. hcho4@uthsc.edu.
AD  - VA Medical Center, Memphis, TN, USA. hcho4@uthsc.edu.
LA  - eng
GR  - Scientific Discovery/Arthritis Foundation/
GR  - MERIT/Biomedical Laboratory Research and Development, VA Office of Research and 
      Development/
GR  - Medical Research Award/Oxnard Foundation (US)/
PT  - Journal Article
DEP - 20190101
PL  - Switzerland
TA  - Inflammopharmacology
JT  - Inflammopharmacology
JID - 9112626
RN  - 0 (Amides)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Collagen Type II)
RN  - 0 (Thiophenes)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1B37H0967P (endothelial PAS domain-containing protein 1)
RN  - 9M632G86CC (2-((aminocarbonyl)amino)-5-(4-fluorophenyl)-3-thiophenecarboxamide)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
SB  - IM
MH  - Amides/*pharmacology
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Basic Helix-Loop-Helix Transcription Factors/metabolism
MH  - Chondrocytes/*drug effects/metabolism
MH  - Collagen Type II/metabolism
MH  - Down-Regulation/drug effects
MH  - Drug Delivery Systems/methods
MH  - Gene Expression/drug effects
MH  - Inflammation/*drug therapy/metabolism
MH  - Matrix Metalloproteinase 13/metabolism
MH  - Osteoarthritis/drug therapy/metabolism
MH  - Signal Transduction/drug effects
MH  - Swine
MH  - Thiophenes/*pharmacology
MH  - Tumor Necrosis Factor-alpha/*metabolism
OTO - NOTNLM
OT  - Chondrocytes
OT  - Inflammation
OT  - Nanosomes
OT  - TNF-alpha
OT  - TPCA-1
OT  - p65 translocation
EDAT- 2019/01/03 06:00
MHDA- 2019/11/28 06:00
CRDT- 2019/01/03 06:00
PHST- 2018/09/04 00:00 [received]
PHST- 2018/10/20 00:00 [accepted]
PHST- 2019/01/03 06:00 [pubmed]
PHST- 2019/11/28 06:00 [medline]
PHST- 2019/01/03 06:00 [entrez]
AID - 10.1007/s10787-018-0542-5 [pii]
AID - 10.1007/s10787-018-0542-5 [doi]
PST - ppublish
SO  - Inflammopharmacology. 2019 Oct;27(5):1011-1019. doi: 10.1007/s10787-018-0542-5. 
      Epub 2019 Jan 1.