| First Author | Myo AC | Year | 2023 |
| Journal | Arch Oral Biol | Volume | 153 |
| Pages | 105753 | PubMed ID | 37348363 |
| Mgi Jnum | J:339779 | Mgi Id | MGI:7524079 |
| Doi | 10.1016/j.archoralbio.2023.105753 | Citation | Myo AC, et al. (2023) Exosome-mediated small interfering RNA delivery inhibits aberrant osteoblast differentiation in Apert syndrome model mice. Arch Oral Biol 153:105753 |
| abstractText | OBJECTIVE: Apert syndrome, an autosomal dominant congenital disorder characterized by craniosynostosis, is caused by a missense mutation (S252W or P253R) in fibroblast growth factor receptor 2 (FGFR2). Exosomes are naturally occurring carriers that deliver nucleic acids, including small interfering RNA (siRNA), to induce gene silencing. This study aimed to develop siRNA-loaded exosomes (Ex-siRNA(Fgfr2S252W)) to silence the Fgfr2(S252W) gain-of-function mutation, thereby inhibiting the increased osteoblastic differentiation caused by the constitutive activation of FGFR2 signaling in calvarial osteoblastic cells isolated from Apert syndrome model mice. DESIGN: Primary calvarial osteoblast-like cells were isolated from the embryonic calvarial sutures of the Apert syndrome model (Fgfr2(S252W/+)) and littermate wild-type mice (Ap-Ob and Wt-Ob, respectively). Exosomes were extracted from the serum of wild-type mice, validated using biomarkers, and used to encapsulate siRNAs. After exosome-mediated siRNA transfection, cells were analyzed under a fluorescence microscope to validate the delivery of Ex-siRNA(Fgfr2S252W), followed by western blot and real-time reverse transcription polymerase chain reaction analyses. RESULTS: After 24 h of Ex-siRNA(Fgfr2S252W) delivery in both Ap-Ob and Wt-Ob, siRNA-loaded exosome delivery was validated. Moreover, p44/42 mitogen-activated protein kinase (MAPK) phosphorylation, runt-related transcription factor 2 (Runx2), and collagen type 1 alpha 1 (Col1a1) mRNA expression, and alkaline phosphatase (ALP) activity were significantly increased in Ap-Ob. The levels of phospho-p44/42 protein, Runx2, Col1a1, and ALP were significantly decreased after Ex-siRNA(Fgfr2S252W) transfection but did not affect Wt-Ob. CONCLUSIONS: These results indicate that exosome-mediated delivery of siRNA targeting Fgfr2(S252W) is a potential non-invasive treatment for aberrant FGF/FGFR signaling. |
