Dual functional nanoparticles containing SOX duo and ANGPT4 shRNA for osteoarthritis treatment
Se-Young Jeong
Integrative Research Institute for Regenerative Medical Engineering, Dongguk University, 814 Siksa-Dong, 411-773 Goyang, Republic of Korea
Search for more papers by this authorMi-Lan Kang
Integrative Research Institute for Regenerative Medical Engineering, Dongguk University, 814 Siksa-Dong, 411-773 Goyang, Republic of Korea
Search for more papers by this authorJeong-Won Park
Integrative Research Institute for Regenerative Medical Engineering, Dongguk University, 814 Siksa-Dong, 411-773 Goyang, Republic of Korea
Search for more papers by this authorCorresponding Author
Gun-Il Im
Integrative Research Institute for Regenerative Medical Engineering, Dongguk University, 814 Siksa-Dong, 411-773 Goyang, Republic of Korea
Correspondence to: G.-I. Im; e-mail: [email protected]Search for more papers by this authorSe-Young Jeong
Integrative Research Institute for Regenerative Medical Engineering, Dongguk University, 814 Siksa-Dong, 411-773 Goyang, Republic of Korea
Search for more papers by this authorMi-Lan Kang
Integrative Research Institute for Regenerative Medical Engineering, Dongguk University, 814 Siksa-Dong, 411-773 Goyang, Republic of Korea
Search for more papers by this authorJeong-Won Park
Integrative Research Institute for Regenerative Medical Engineering, Dongguk University, 814 Siksa-Dong, 411-773 Goyang, Republic of Korea
Search for more papers by this authorCorresponding Author
Gun-Il Im
Integrative Research Institute for Regenerative Medical Engineering, Dongguk University, 814 Siksa-Dong, 411-773 Goyang, Republic of Korea
Correspondence to: G.-I. Im; e-mail: [email protected]Search for more papers by this authorAbstract
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. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:234–242, 2020.
Supporting Information
| Filename | Description |
|---|---|
| jbmb34383-Sup-0001-FigS1.tifTIFF image, 139.9 KB | FIGURE S1 Results of gel retardation assays performed to determine the concentration of DEXPEI copolymer that could retard MCSOX9/6/shANG DNA. |
| jbmb34383-Sup-0002-FigS2.tifTIFF image, 289 KB | FIGURE S2 Dose-dependent in vitro cytotoxicities of DEXPEI and TDPEI in ADSCs as determined by CCK assays (A) and Live/Dead cell staining counts (B). Results are presented as means ± SDs (N = 3). |
| jbmb34383-Sup-0003-FigS3.tifTIFF image, 122.1 KB | FIGURE S3 MTT cell proliferation assay of ADSCs incubated for 1 and 7 days with different concentrations of DEXPEI. |
| jbmb34383-Sup-0004-FigS4.tifTIFF image, 3.4 MB | FIGURE S4 Hematoxylin and eosin staining of each group of surgically-induced OA rats 8 weeks after first injection (A). Immunohistochemistry for COL10 of in vitro samples from Figure 3(B-a) and in vivo samples from Figure 4(B-b). |
| jbmb34383-Sup-0005-FigS5.tifTIFF image, 762.3 KB | FIGURE S5 In vivo tracking of MCSOX9/6/shANG-transfected ADSCs at various time points that were injected into right knee joints of surgically-induced OA rats. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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