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Background <p>Medication-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.</p> Methods <p>Transcriptome 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).</p> Results <p>miR-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.</p> Conclusions <p>The 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.</p>

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Localized therapeutic strategy based on microRNA-21-loaded mesoporous silica nanoparticles hydrogel improves bone repair in medication-related osteonecrosis of the jaw

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月23日

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  • Ye Li,
  • Siyuan Huang,
  • Yihan Xing,
  • Zhuofan Chen,
  • Dongsheng Yu

摘要

Background

Medication-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.

Methods

Transcriptome 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).

Results

miR-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.

Conclusions

The 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.