# MSC Membrane‐Coated circPROSC‐siRNA Nanoparticles for Ameliorating Craniosynostosis by Inhibiting Premature Suture Ossification

## TL;DR

This study identifies circPROSC as a key factor in craniosynostosis and shows that targeting it with nanoparticles can reduce premature skull suture closure.

## Contribution

The study introduces circPROSC as a novel diagnostic biomarker and therapeutic target for craniosynostosis.

## Key findings

- circPROSC promotes osteogenesis via miR-6815-5p-mediated activation of the Wnt signaling pathway.
- MSC membrane-coated siRNA nanoparticles targeting circPROSC reduce premature suture closure in a mouse model.
- circPROSC functions as a sponge for miR-6815-5p, enhancing RUNX2-mediated osteogenesis.

## Abstract

Craniosynostosis is a congenital craniofacial disorder caused by excessive osteogenic differentiation of mesenchymal stem cells (MSCs) within cranial sutures. Due to incompletely understood regulatory mechanisms, effective solutions for early diagnosis and minimally invasive therapy remain lacking. In this study, plsama circPROSC is first identified as an independent risk factor for craniosynostosis. Through MSCs osteogenic differentiation and nude mouse ectopic bone formation assays, circPROSC promotes osteogenesis via miR‐6815‐5p‐mediated modulation of the Wnt signaling pathway. Furthermore, MSC membrane‐coated siRNA nanoparticles (MM@Lipo/siRNA) targeting circPROSC (si‐circPROSC) have been developed to inhibit its expression in the coronal suture by postnatal cranial microinjection, which attenuated premature coronal suture closure in a craniosynostosis mouse model. Collectively, this study provides the first evidence that circPROSC is a promising diagnostic marker and a potential therapeutic target for craniosynostosis.

CircPROSC promotes craniosynostosis by sponging miR‐6815‐5p, thereby activating WNT3A/β‐catenin signaling and enhancing RUNX2‐mediated osteogenesis. Targeted silencing of circPROSC with MSC membrane–coated siRNA nanoparticles (MM@Lipo/si‐circPROSC) delivered postnatally into cranial sutures attenuates premature suture closure in Twist1+/– mice, highlighting circPROSC as a novel diagnostic biomarker and therapeutic target.