The effect of local delivery of adiponectin from biodegradable microsphere–scaffold composites on new bone formation in adiponectin knockout mice
Autor: | Zi-Chen Li, Hui Lu, Xue-fen Li, Dan Li, Yuan Guo, Songhe Lu, Hongcheng Hu, Zhihui Tang, Ren Wang, Yuwei Wu |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Small interfering RNA Materials science Adiponectin Biomedical Engineering Osteoblast General Chemistry General Medicine Bone remodeling Cell biology Pleckstrin homology domain 03 medical and health sciences 030104 developmental biology medicine.anatomical_structure Endocrinology Downregulation and upregulation Internal medicine Knockout mouse medicine General Materials Science PI3K/AKT/mTOR pathway |
Zdroj: | Journal of Materials Chemistry B. 4:4771-4779 |
ISSN: | 2050-7518 2050-750X |
Popis: | Adiponectin (APN) is the most abundant adipocyte-secreted adipokine; it regulates energy homeostasis and exerts well-characterized insulin-sensitizing properties. Previous studies have verified that globular adiponectin (gAPN) is also involved in bone metabolism, although observations have been controversial. The purpose of the current study is to use an APN-knockout (APN-KO) mouse model to evaluate the local delivery of gAPN to new bone formation. Using chitosan microspheres (CMs), we found that following an initial burst at 1 week, the release behavior of gAPN from the scaffold was sustained in a linear manner for the first 4 weeks, followed by a slower, more stable release from week 5 onwards. Interestingly, PLGA/β-TCP/CM-loaded gAPN scaffolds implanted in APN-KO mice increased bone formation and mineralization, and enhanced osteogenic marker expression 28 days post-implantation. gAPN also promoted preosteoblast (MC3T3-E1) cellular proliferation in vitro. In MC3T3-E1 cells, adaptor protein-containing pleckstrin homology domain, phosphotyrosine domain, leucine zipper motif (APPL1) and phosphoinositide 3-kinase (PI3K) expression was upregulated in a time-dependent manner upon gAPN treatment, while APPL1 small interfering RNA (siRNA) pre-treatment reversed this enhanced expression. In conclusion, modified bone graft substitutes loaded with gAPN increase bone formation and mineralization in part by promoting osteoblast proliferation via the APPL1/PI3K pathway. |
Databáze: | OpenAIRE |
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