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Effect of nanoparticle-mediated delivery of SFRP4 siRNA for treating Dupuytren disease

Gene Therapy volume 30, pages 31–40 (2023)Cite this article

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Abstract

Dupuytren disease (DD) is a progressive fibrous proliferative disease. It invades the palmar aponeurosis and extends to the finger fascia, eventually leading to flexion contracture of the metacarpophalangeal or interphalangeal joint. At present, surgical resection and the local injection of collagenase are the main methods for the treatment of DD, but postoperative complications and high recurrence rates often occur. Bioinformatics analysis showed that the increased expression of SFRP4 protein was closely related to the incidence of DD. Persistent and effective inhibition of SFRP4 expression may be a promising treatment for DD. We prepared SFRP4 siRNA/nanoparticle complexes (si-SFRP4) and negative siRNA/nanoparticle complexes (NC) and applied them in vitro and in vivo. Flow cytometry analysis showed that si-SFRP4 could be successfully transfected into DD cells. MTT and EdU staining assays showed that the OD values and percentage of EdU-positive cells in the si-SFRP4 group were significantly lower than those in the NC group. Scratch tests showed that the wound healing rate of the si-SFRP4 group was lower than that of the NC group, and the difference was statistically significant. The expression of SFRP4 and α-SMA protein in the si-SFRP4 group significantly decreased in both DD cells and xenografts. Compared with the NC group, the xenograft quality of the si-SFRP4 group was significantly reduced. Masson’s trichrome staining showed that the collagen and fibrous cells in the si-SFRP4 group were more uniform, slender, parallel and regular. The above experimental results suggest that the proliferation and metabolism of palmar aponeurosis cells and the quality of metacarpal fascia xenografts were both significantly decreased. We speculated that nanoparticle-mediated SFRP4 siRNA can be used as a potential new method for the treatment of DD.

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Fig. 1: Morphological and histological features of normal or contractural palmar aponeurosis tissues.
Fig. 2: Bioinformatics analysis and experimental verification of differentially expressed genes between normal or contractural palmar aponeurosis tissues.
Fig. 3: Preparation, characteristics and transfection effciency of siRNA/nanoparticle complexes.
Fig. 4: Effect of si-SFRP4/nanoparticle complexes on dupuytren disease cells in vitro.
Fig. 5: Therapy effect of si-SFRP4/nanoparticle complexes on dupuytren disease in vivo.

Data availability

The datasets generated during and/or analyzed during the current study are available in the [NCBI] repository, [https://www.ncbi.nlm.nih.gov/sra]. The additional data generated during and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was financially supported by Technology Projects of Nantong (No. MS12019022).

Funding

This study was funded by Technology Projects of Nantong (No. MS12019022).

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  1. These authors contributed equally: Rujue Jin, Weigang Zhu.

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  1. Department of Hand Surgery, Hand Surgery Research Center, Affiliated Hospital of Nantong University, Nantong, 226001, PR China

    Rujue Jin, Weigang Zhu, Jianhui Gu & Aidong Deng

  2. Department of Orthopedics, Affiliated Rugao Hospital of Nantong University, Nantong, 226500, PR China

    Jiajun Xu

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All authors were responsible for conceiving and designing the review protocol, acquiring and analyzing data, interpreting results. RJJ and WGZ were responsible for conducting the search, drafting the manuscript and updating reference lists. ADD and JHG were responsible for revising the report. All authors approved the final version and agreed to be accountable for all aspects of the work.

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Jin, R., Zhu, W., Xu, J. et al. Effect of nanoparticle-mediated delivery of SFRP4 siRNA for treating Dupuytren disease. Gene Ther 30, 31–40 (2023). https://doi.org/10.1038/s41434-022-00330-9

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