PMID- 25639048
OWN - NLM
STAT- MEDLINE
DCOM- 20150717
LR  - 20181202
IS  - 1002-1892 (Print)
IS  - 1002-1892 (Linking)
VI  - 28
IP  - 11
DP  - 2014 Nov
TI  - [Phosphorylatable short peptide conjugated chitosan mediated gene therapy for 
      repair of articular cartilage defect in rabbits].
PG  - 1346-52
AB  - OBJECTIVE: To investigate the effect of phosphorylatable short peptide ((P)SP) 
      conjugated chitosan (CS) ((P)SP-CS)mediated insulin-like growth factor 1 (IGF-1) 
      gene and human interleukin 1 receptor antagonist (IL-1Ra) gene local transfection 
      on the repair of articular cartilage defect. METHODS: Co-expression plasmid 
      pBudCE4.1-IL-1Ra + IGF-1, single gene expression plasmid pBudCE4.1-IL-1Ra and 
      pBudCE4.1-IGF-1 were constructed and combined with (P)SP-CS to form (P)SP-CS/pDNA 
      complexes. Thirty 3-month-old healthy male New Zealand white rabbits, weighing 
      2.0-2.5 kg, double legs were randomly divided into 5 groups (n = 12). Lateral 
      femoral condyle articular surface was only exposed in sham-operated group (group 
      A); full-thickness cartilage defects were created in the articular surface of the 
      lateral femoral condyle of the knee in 4 intervention groups: (P)SP-CS/pBudCE4.1 
      (group B), (P)SP-CS/pBudCE4.1-IL-1Ra (group C), (P)SP-CS/pBudCE4.1-IGF-1 (group 
      D), and (P)SP-CS/pBudCE4.1-IL-1Ra + IGF-1 (group E). At 1 week after operation, 
      intra-articular injection of (P)SP-CS/pDNA complexes was administrated 2 times a 
      week for 7 weeks in each intervention group, the same volume normal saline in 
      group A. The general condition of animal was observed after operation, and 
      rabbits were sacrificed at 8 weeks. Knee joint synovial fluid was collected to 
      measure the concentrations of the IL-1Ra and IGF-1 by ELISA; mRNA expressions of 
      Aggrecan, matrix metalloproteinase 3 (MMP-3), and MMP inhibitor 1 (TIMP-1) were 
      detected by real-time fluorescent quantitative PCR; the chondrogenic phenotype of 
      nascent cells in the damage zone was identified by alcian blue-periodic 
      acid/schiff (AB-PAS) histochemistry and Aggrecan immunohistochemistry staining. 
      RESULTS: Thirty experimental rabbits all survived to the end of experiment, 
      without infection and death. Large amounts of exogenous proteins of IGF-1 and 
      IL-1Ra were detected in the synovial fluid of 4 intervention groups. There were 
      significant differences between groups D, E and group A in IGF-1 protein 
      expression, and between goups C, E and group A in IL-1Ra protein expression (P < 
      0.05). Aggrecan and TIMP-1 mRNA expressions were significantly up-regulated in 
      group E, simultaneously MMP-3 mRNA expression was significantly down-regulated 
      when compared with groups C and D (P < 0.05). Varying degrees of cartilage repair 
      appeared in groups C, D, and E, showing positive staining of AB-PAS and Aggrecan, 
      and group E had better results than groups C and D (P < 0.05); inflammatory cell 
      infiltration and fibrous tissue proliferation were seen in the defect region of 
      group B, without significant cartilage repairing. CONCLUSION: (P)SP-CS is an 
      ideal gene delivery system for cartilage defect gene therapy; IL-1Ra and IGF-1 
      double gene transfection has better biologic effect on cartilage defect repair.
FAU - Zhao, Ronglan
AU  - Zhao R
FAU - Peng, Xiaoxiang
AU  - Peng X
FAU - Chu, Hairong
AU  - Chu H
FAU - Song, Wei
AU  - Song W
LA  - chi
PT  - Journal Article
PL  - China
TA  - Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
JT  - Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = 
      Chinese journal of reparative and reconstructive surgery
JID - 9425194
RN  - 0 (Aggrecans)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (Peptides)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 9012-76-4 (Chitosan)
SB  - IM
MH  - Aggrecans/metabolism
MH  - Animals
MH  - Cartilage
MH  - Cartilage, Articular/*drug effects/injuries/pathology
MH  - Chitosan/*administration & dosage/therapeutic use
MH  - Gene Transfer Techniques
MH  - *Genetic Therapy
MH  - Humans
MH  - Injections, Intra-Articular
MH  - Insulin-Like Growth Factor I/genetics/metabolism
MH  - Knee Joint
MH  - Male
MH  - Matrix Metalloproteinase Inhibitors
MH  - Peptides
MH  - Rabbits
MH  - Synovial Fluid/*metabolism
MH  - Tissue Engineering/*methods
MH  - Tissue Inhibitor of Metalloproteinase-1/genetics/metabolism
MH  - Transfection
MH  - Wound Healing
EDAT- 2015/02/03 06:00
MHDA- 2015/07/18 06:00
CRDT- 2015/02/03 06:00
PHST- 2015/02/03 06:00 [entrez]
PHST- 2015/02/03 06:00 [pubmed]
PHST- 2015/07/18 06:00 [medline]
PST - ppublish
SO  - Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2014 Nov;28(11):1346-52.