ArticleJournal of orthopaedic surgery and research2025
Localized therapeutic strategy based on microRNA-21-loaded mesoporous silica nanoparticles hydrogel improves bone repair in medication-related osteonecrosis of the jaw.
Article in Journal of orthopaedic surgery and research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundMedication-related osteonecrosis of the jaw (MRONJ), caused by long-term anti-resorptive therapy, leads to bone necrosis and impaired healing. This study developed a miR-21-loaded mesoporous silica nanoparticles (MSN) hydrogel to promote local bone regeneration.
methodsTranscriptome sequencing of zoledronic acid (ZOL)-treated osteoclasts (OCs) revealed PDCD4 upregulation and NF-κB (p65) phosphorylation inhibition. miR-21, identified as a regulator of PDCD4, was validated in vitro. Amino-modified mesoporous silica nanoparticles (MSN-NH₂) were synthesized to carry miR-21, and embedded in a dynamic Schiff base-crosslinked hydrogel. The hydrogel's biocompatibility, sustained release, and therapeutic effect were evaluated in a rat MRONJ model via micro-CT, histology, TRAP staining, and RNA in situ hybridization (RISH).
resultsmiR-21 reversed ZOL-induced suppression of NF-κB/p65 phosphorylation by targeting PDCD4, thereby restoring osteoclast differentiation and resorption activity. The miR-21-loaded MSN hydrogel promoted bone regeneration, increased TRAP⁺ osteoclast numbers, and elevated local miR-21 expression, while maintaining systemic safety. These findings suggest that the miR-21-loaded MSN hydrogel system exerts its therapeutic effect primarily through the miR-21/PDCD4/NF-κB signaling pathway, facilitating coordinated regulation of osteoclast-mediated bone remodeling.
conclusionsThe miR-21-loaded MSN hydrogel effectively restored bone remodeling and healed MRONJ defects without systemic toxicity, offering a promising localized adjunct to anti-resorptive therapies.
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