Dual functional nanoparticles containing SOX duo and ANGPT4 shRNA for osteoarthritis treatment

Se Young Jeong, Mi Lan Kang, Jeong Won Park, Gun Il Im

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

In our previous studies, we found that adult stem cells transfected with sex-determining region Y-box (SOX)-9, -6 and -5 genes (SOX trio) enhanced chondrogenesis and suppressed the progression of osteoarthritis (OA). The inhibition of angiopoietin-like 4 (ANGPT4) is known to reduce levels of cartilage damaging enzymes, such as, matrix metalloproteinases (MMPs). In this study, we designed nanoparticles comprising dexamethasone-conjugated polyethylenimine (DEXPEI) complexed with minicircle plasmid (MC) harboring SOX duo (SOX-9, -6) and ANGPTL4 small hairpin RNA (shANG) [MCSOX9/6/shANG] in the expectation that transfection of these nanoparticles would enhance chondrogenesis of stem cells and suppress inflammation in OA. Adipose-derived stem cells (ADSCs) transfected with MCSOX9/6/shANG (MCSOX9/6/shANG-tADSCs) showed significantly higher expressions of COL2 gene and protein than MCSOX9/6-transfected ADSCs (MCSOX9/6-tADSCs) during in vitro chondrogenesis while both enhanced chondrogenesis in the absence of growth factor addition as compared with negative controls. Furthermore, the expressions of MMP13 and MMP3 genes were significantly more diminished in MCSOX9/6/shANG-tADSCs than in MCSOX9/6-tADSCs. In vivo experiments using surgically-induced OA rats showed MCSOX9/6/shANG-tADSC-treated rats had significantly lower levels of cyclooxygenase (COX-2) and MMP13 in synovial fluids than MCSOX9/6-tADSC-treated rats, but no significant difference was observed between them in histological appearances. Both groups showed significantly less joint destruction than control groups did. These results demonstrate that dual functional nanoparticles containing SOX duo and ANGPT4 shRNA enhance chondrogenesis of ADSCs and suppress inflammation in OA.

Original languageEnglish
Pages (from-to)234-242
Number of pages9
JournalJournal of Biomedical Materials Research - Part B Applied Biomaterials
Volume108
Issue number1
DOIs
StatePublished - 1 Jan 2020

Keywords

  • SOX duo
  • angiopoietin-like 4
  • chondrogenesis
  • gene therapy
  • osteoarthritis

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