title: Exogenous expression of IL-1Ra and TGF-β1 promotes in vivo repair in experimental rabbit osteoarthritis.
abstract: OBJECTIVE
  Potential gene therapy application of single and co-expression of interleukin 1 (IL-1) receptor antagonist (IL-1Ra) and transforming growth factor-β1 (TGF-β1) to alter disease progression was investigated in an in-vivo rabbit model of osteoarthritis (OA).
  
  
  METHODS
  Sixteen young adult rabbits were randomly and equally divided into four groups: blank control group, IL-1Ra transfection group, TGF-β1 transfection group, and IL-1Ra/TGF-β1 double transfection group. Histological examinations were performed to monitor disease progression after haematoxylin and eosin (H&E) staining of articular cartilage. Immunohistochemistry was used to detect IL-1Ra and TGF-β1 in synovial membrane tissues. Exogenous IL-1Ra and TGF-β1 content was assessed in joint lavage fluid using an enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  ELISA measurements from the joint lavage fluid showed high expressions of IL-1Ra and TGF-β1 in the single and double transfection groups. Remarkably, concomitant reductions in IL-1β and tumour necrosis factor alpha (TNF-α) levels were observed in these single and double transfection groups. Radioimmunoassay (RIA)-based detection showed that IL-1β and TNF-α levels in the gene transfection groups were significantly lower compared to the blank control group, in parallel experiments. Importantly, injection of IL-1Ra and TGF-β1 expressing cartilage cells into joints led to a significant inhibition of cartilage matrix degradation. Finally, IL-1Ra and TGF-β1 expression in tissues correlated with disease reversal in the experimental group, with improved tissue architecture and collagen deposition.
  
  
  CONCLUSIONS
  Our results reveal that both single- and double-gene transfection of IL-1Ra and TGF-β1 promote extensive repair of damaged cartilage, and double transfections showed better recovery than single transfections, suggesting that co-expression of IL-1Ra and TGF-β1 inhibits degeneration and improves repair of articular cartilage in OA.
authors.affiliation: a Department of Orthopaedics, the Third Affiliated Hospital , Guangzhou Medical University , Guangzhou , P. R. China.
authors.forename: P
authors.initials: P
authors.lastname: Zhang
authors.affiliation: a Department of Orthopaedics, the Third Affiliated Hospital , Guangzhou Medical University , Guangzhou , P. R. China.
authors.forename: Z-H
authors.initials: ZH
authors.lastname: Zhong
authors.affiliation: a Department of Orthopaedics, the Third Affiliated Hospital , Guangzhou Medical University , Guangzhou , P. R. China.
authors.forename: H-T
authors.initials: HT
authors.lastname: Yu
authors.affiliation: b Department of Orthopaedics, the Third Affiliated Hospital , Sun Yat-Sen University , Guangzhou , P. R. China.
authors.forename: B
authors.initials: B
authors.lastname: Liu
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005240:Feasibility Studies; D005786:Gene Expression Regulation / Q000502:physiology*; D015316:Genetic Therapy / Q000379:methods*; D007267:Injections; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics* / Q000378:metabolism; D008081:Liposomes; D010003:Osteoarthritis / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D011817:Rabbits; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D008081:Liposomes; D053773:Transforming Growth Factor beta1