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Updated: Sep 6, 2025

A Novel in vivo Gene Transfer Technique and in vitro Cell Based Assays for the Study of Bone Loss in Musculoskeletal Disorders
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Suppression of osteoclast multinucleation via a posttranscriptional regulation-based spatiotemporally selective

Qingqing Wang1,2, Haoli Wang1,2, Huige Yan1,2

  • 1Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, Zhejiang 310016, China.

Science Advances
|June 29, 2022
PubMed

Insights

Excessive osteoclast fusion causes bone disease. Researchers developed targeted nanoparticles delivering circBBS9 RNA to preosteoclasts, offering a new strategy to control multinucleated cell formation and treat related diseases.

Area of Science:

  • Biomedical Engineering
  • Molecular Biology
  • Cell Biology

Background:

  • Multinucleated osteoclasts, formed by excessive preosteoclast (pOC) fusion, contribute to osteolytic diseases like osteoporosis.
  • Current treatments non-selectively inhibit osteoclasts, disrupting bone homeostasis.
  • Targeting pOCs offers a more precise approach to bone health regulation.

Purpose of the Study:

  • To identify novel regulators of osteoclast formation.
  • To develop a targeted delivery system for therapeutic RNA in pOCs.
  • To investigate the circBBS9/miR-423-3p/Traf6 axis in pOCs.

Main Methods:

  • Identification of circBBS9 as a regulator in pOCs.
  • Construction of biomimetic nanoparticles (POCM-NPs) camouflaged with pOC membranes.
  • Loading nanoparticles with siRNA/shRNA targeting circBBS9 (POCM-NPs@siRNA/shRNAcircBBS9) for targeted delivery.

Main Results:

  • POCM-NPs demonstrated enhanced stability, specific pOC targeting, and efficient cellular uptake.
  • The nanoparticles exhibited reactive oxygen species-responsive release of their cargo.
  • The circBBS9/miR-423-3p/Traf6 axis was confirmed to regulate pOCs.

Conclusions:

  • A novel circRNA, circBBS9, plays a role in pOC regulation via a specific molecular axis.
  • Biomimetic nanoparticles enable spatiotemporally controlled delivery of RNA therapeutics to pOCs.
  • This targeted delivery system presents a promising strategy for managing diseases characterized by excessive multinucleated cell formation.

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