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Article Abstract

Purpose: Locked nucleic acid (LNA)-modified anti-microRNAs have been demonstrated to target mesenchymal stem cells (MSCs) to treat bone diseases. However, the "off-target" effect limits its clinical application.

Methods: We selected specific aptamer M4 of MSCs and employed the three-way junction (3WJ) as the core scaffold to construct nanoparticles (3WJ-M4-LNA) for specific delivery of anti-miRNA 138.

Results: Our results suggested that the 3WJ-M4-LNA nanoparticles, not 3WJ-M4 or 3WJ-LNA, can specifically deliver anti-miRNA to MSCs, resulting in significant inhibition of miRNA 138 expression. Our experiment further confirmed that the nanoparticles can promote MSCs' osteogenic differentiation by activating the ERK1/2 pathway. In vivo, the nanoparticles promoted bone formation and improved the bone microarchitecture in rabbit osteoporosis models.

Conclusions: These results indicate that the 3WJ nanoparticles could develop as a specific therapeutic strategy for osteoporosis.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923633PMC
http://dx.doi.org/10.1021/acsomega.4c11505DOI Listing

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