PMID- 30276528
OWN - NLM
STAT- MEDLINE
DCOM- 20190716
LR  - 20190716
IS  - 1573-4838 (Electronic)
IS  - 0957-4530 (Print)
IS  - 0957-4530 (Linking)
VI  - 29
IP  - 10
DP  - 2018 Oct 1
TI  - Chitosan/hyaluronic acid/plasmid-DNA nanoparticles encoding interleukin-1 
      receptor antagonist attenuate inflammation in synoviocytes induced by 
      interleukin-1 beta.
PG  - 155
LID - 10.1007/s10856-018-6160-3 [doi]
LID - 155
AB  - Synovial inflammation mainly resulting from interleukin-1 beta (IL-1beta) plays a 
      crucial role in the early and late stage of osteoarthritis. Recent progress in 
      therapeutic gene delivery systems has led to promising strategies for local 
      sustained target gene expression. The aim of this study was to design a 
      nanoparticle made of chitosan (CS)/hyaluronic acid (HA)/plasmid-DNA (pDNA) 
      encoding IL-1 receptor antagonist gene (pIL-1Ra) and furtherly use it to 
      transfect the primary synoviocytes, and then investigate whether CS/HA/pIL-1Ra 
      nanoparticles could make the synoviocytes overexpress functional IL-1Ra to 
      attenuate inflammation induced by IL-1beta. In this study, CS was modified with HA 
      to generate CS/HA nanoparticles and then combined with pIL-1Ra to form 
      CS/HA/pIL-1Ra nanoparticles. The physicochemical characteristics results showed 
      that CS/HA nanoparticles exhibited an appropriate particle size (144.9 +/- 2.8 nm) 
      and positive zeta potential ( + 28 mV). The gel retardation assay revealed that 
      pDNA was effectively protected and released in a sustained manner more than 15 
      days. Cytotoxicity results showed that CS/HA/pIL-1Ra nanoparticles had a safe 
      range (0-80 mug/ml) for the application to synoviocytes. RT-qPCR and western blot 
      analysis demonstrated that CS/HA/pIL-1Ra nanoparticles were able to increase 
      IL-1Ra expression in primary synoviocytes, and reduce the mRNA and protein levels 
      of matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-13 (MMP-13), 
      cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in 
      IL-1beta-induced synoviocytes. Our findings indicated that CS/HA/pIL-1Ra 
      nanoparticles efficiently transfected synoviocytes and attenuated synovitis 
      induced by IL-1beta, which will provide a potential strategy for OA synovitis.
FAU - Deng, Rong-Hui
AU  - Deng RH
AD  - Department of Orthopedics, Renmin Hospital of Wuhan University, Ziyang Road 99, 
      Wuhan, 430060, China.
FAU - Qiu, Bo
AU  - Qiu B
AD  - Department of Orthopedics, Renmin Hospital of Wuhan University, Ziyang Road 99, 
      Wuhan, 430060, China.
FAU - Zhou, Pang-Hu
AU  - Zhou PH
AUID- ORCID: 0000-0002-7020-4258
AD  - Department of Orthopedics, Renmin Hospital of Wuhan University, Ziyang Road 99, 
      Wuhan, 430060, China. zhoupanghu@126.com.
LA  - eng
GR  - 81501921/National Natural Science Foundation of China/
GR  - 2016CFB500/Natural Science Foundation of Hubei Province/
GR  - 2016060101010045/Wuhan Science and Technology Project of China/
GR  - 2015BCA316/Hubei Provincial Science and Technology Support Program of China/
PT  - Journal Article
DEP - 20181001
PL  - United States
TA  - J Mater Sci Mater Med
JT  - Journal of materials science. Materials in medicine
JID - 9013087
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
RN  - 0 (Interleukin-1beta)
RN  - 9004-61-9 (Hyaluronic Acid)
RN  - 9007-49-2 (DNA)
RN  - 9012-76-4 (Chitosan)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Animals
MH  - Cell Survival
MH  - Chitosan/*chemistry
MH  - Cyclooxygenase 2/metabolism
MH  - DNA/*chemistry
MH  - Gene Transfer Techniques
MH  - Hyaluronic Acid/*chemistry
MH  - Inflammation/metabolism
MH  - Interleukin 1 Receptor Antagonist Protein/genetics/*metabolism
MH  - Interleukin-1beta/*pharmacology
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Nanoparticles/*chemistry
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Particle Size
MH  - Plasmids
MH  - Rats, Sprague-Dawley
MH  - Synoviocytes/*metabolism
PMC - PMC6182723
COIS- The authors declare that they have no conflict of interest.
EDAT- 2018/10/03 06:00
MHDA- 2019/07/17 06:00
PMCR- 2018/10/01
CRDT- 2018/10/03 06:00
PHST- 2018/01/02 00:00 [received]
PHST- 2018/09/18 00:00 [accepted]
PHST- 2018/10/03 06:00 [entrez]
PHST- 2018/10/03 06:00 [pubmed]
PHST- 2019/07/17 06:00 [medline]
PHST- 2018/10/01 00:00 [pmc-release]
AID - 10.1007/s10856-018-6160-3 [pii]
AID - 6160 [pii]
AID - 10.1007/s10856-018-6160-3 [doi]
PST - epublish
SO  - J Mater Sci Mater Med. 2018 Oct 1;29(10):155. doi: 10.1007/s10856-018-6160-3.