A blood glucose fluctuation-responsive delivery system promotes bone regeneration and the repair function of Smpd3-reprogrammed BMSC-derived exosomes  

作　　者：Lingxiao Wang Haoqing Yang Chen Zhang Yue Zhang Yilin He Yang Liu Pan Ma Jun Li Zhipeng Fan 

机构地区：[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]Beijing Laboratory of Oral Health,Capital Medical University,Beijing,China [5]Research Unit of Tooth Development and Regeneration,Chinese Academy of Medical Sciences,Beijing,China

出　　处：《International Journal of Oral Science》2024年第4期782-796,共15页国际口腔科学杂志(英文版)

基　　金：supported by the National Key Research and Development Program(2022YFA1104401);CAMS Innovation Fund for Medical Sciences(2019-I2M-5-031 to Z.P.F.);grants from Innovation Research Team Project of Beijing Stomatological Hospital,Capital Medical University(No.CXTD202204 to Z.P.F.);the National Natural Science Foundation of China(No.82401155 to L.X.W.);R&D Program of Beijing Municipal Education Commission(KM202410025007);Training Fund for Open Projects at Clinical Institutes and Departments of Capital Medical University(CCMU2024ZKYXZ002);the Young Scientist Program of Beijing Stomatological Hospital,Capital Medical University,No.YSP202208。

摘　　要：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 glucosefluctuating 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 Smpd3overexpression 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.

关 键 词：Blood FUNCTION promoted 

分 类 号：R587.2[医药卫生—内分泌] R782[医药卫生—内科学]