DP7-C/mir-26a system promotes bone regeneration by remodeling the osteogenic immune microenvironment.

Huang, Jie; Yang, Yiling; Zhu, Yushu; Xiao, Xun; Yalikun, Kaidiliya; Jiang, Xiliang; Yang, Li; Mu, Yandong

Huang, Jie; Yang, Yiling; Zhu, Yushu; Xiao, Xun; Yalikun, Kaidiliya; Jiang, Xiliang; Yang, Li; Mu, Yandong.

Afiliação

Huang J; Department of Stomatology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Yang Y; General Dentistry, Chongqing University Three Gorges Hospital, Chongqing, China.
Zhu Y; Department of Stomatology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Xiao X; Department of Stomatology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Yalikun K; Department of Stomatology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Jiang X; Department of Stomatology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Yang L; Department of Stomatology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Mu Y; State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Oral Dis ; 2024 Mar 19.

Article em En | MEDLINE | ID: mdl-38501171

ABSTRACT

ABSTRACT

OBJECTIVE:

This study investigates the DP7-C/miR-26a complex as a stable entity resulting from the combination of miR-26a with the immunomodulatory peptide DP7-C. Our focus is on utilizing DP7-C loaded with miR-26a to modulate the immune microenvironment in bone and facilitate osteogenesis.

METHODS:

The DP7-C/miR-26a complex was characterized through transmission electron microscopy, agarose electrophoresis, and nanoparticle size potentiometer analysis. Transfection efficiency and cytotoxicity of DP7-C were assessed using flow cytometry and the CCK-8 assay. We validated the effects of DP7-C/miR-26a on bone marrow mesenchymal stem cells (BMSCs) and macrophages RAW 264.7 through gene expression and protein synthesis assays. A comprehensive evaluation of appositional bone formation involved micro-CT imaging, histologic analysis, and immunohistochemical staining.

RESULTS:

DP7-C/miR-26a, a nanoscale, and low-toxic cationic complex, demonstrated the ability to enter BMSCs and RAW 264.7 via distinct pathways. The treatment with DP7-C/miR-26a significantly increased the synthesis of multiple osteogenesis-related factors in BMSCs, facilitating calcium nodule formation in vitro. Furthermore, DP7-C/miR-26a promoted M1 macrophage polarization toward M2 while suppressing the release of inflammatory factors. Coculture studies corroborated these findings, indicating significant repair of rat skull defects following treatment with DP7-C/miR-26a.