A blood glucose fluctuation-responsive delivery system promotes bone regeneration and the repair function of Smpd3-reprogrammed BMSC-derived exosomes.
10.1038/s41368-024-00328-6
- Author:
Lingxiao WANG
1
;
Haoqing YANG
1
;
Chen ZHANG
1
;
Yue ZHANG
2
;
Yilin HE
3
;
Yang LIU
1
;
Pan MA
3
;
Jun LI
3
;
Zhipeng FAN
4
Author Information
1. Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory for Tooth Regeneration and Function Reconstruction of Oral Tissues, School of Stomatology, Beijing Stomatological Hospital, Capital Medical University, Beijing, China.
2. Department of Periodontics, School of Stomatology, Beijing Stomatological Hospital, Capital Medical University, Beijing, China.
3. Department of Dental Implant Center, School of Stomatology, Beijing Stomatological Hospital, Capital Medical University, Beijing, China.
4. Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory for Tooth Regeneration and Function Reconstruction of Oral Tissues, School of Stomatology, Beijing Stomatological Hospital, Capital Medical University, Beijing, China. zpfan@ccmu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Exosomes;
Animals;
Bone Regeneration/drug effects*;
Dogs;
Mesenchymal Stem Cells;
Humans;
Blood Glucose;
Cell Differentiation;
Osteogenesis/drug effects*;
Diabetes Mellitus, Type 2/therapy*;
Diabetes Mellitus, Experimental;
Cells, Cultured;
Hydrogels;
Male
- From:
International Journal of Oral Science
2024;16(1):65-65
- CountryChina
- Language:English
-
Abstract:
Blood glucose fluctuation leads to poor bone defect repair in patients with type 2 diabetes (T2DM). Strategies to safely and efficiently improve the bone regeneration disorder caused by blood glucose fluctuation are still a challenge. Neutral sphingophospholipase 2 (Smpd3) is downregulated in jawbone-derived bone marrow mesenchymal stem cells (BMSCs) from T2DM patients. Here, we investigated the effect of Smpd3 on the osteogenic differentiation of BMSCs and utilized exosomes from stem cells overexpressing Smpd3 as the main treatment based on the glucose responsiveness of phenylboronic acid-based polyvinyl alcohol crosslinkers and the protease degradability of gelatin nanoparticles. The combined loading of Smpd3-overexpressing stem cell-derived exosomes (Exos-Smpd3) and nanosilver ions (Ns) to construct a hydrogel delivery system (Exos-Smpd3@Ns) promoted osteogenesis and differentiation of BMSCs in a glucose-fluctuating environment, ectopic osteogenesis of BMSCs in a glucose-fluctuating environment and jawbone regeneration of diabetic dogs in vitro. Mechanistically, Smpd3 promoted the osteogenesis and differentiation of jawbone-derived BMSCs by activating autophagy in the jawbone and inhibiting macrophage polarization and oxidative stress caused by blood glucose fluctuations. These results reveal the role and mechanism of Smpd3 and the Smpd3 overexpression exosome delivery system in promoting BMSC function and bone regeneration under blood glucose fluctuations, providing a theoretical basis and candidate methods for the treatment of bone defects in T2DM patients.
