MiR-6924-5p-rich exosomes derived from genetically modified Scleraxis-overexpressing PDGFRα(+) BMMSCs as novel nanotherapeutics for treating osteolysis during tendon-bone healing and improving healing strength
| Autor: | Zhou Mei, Kang Xia, Wang Huan, Tang Kang-lai, Bian Xu-Ting, Huang Pan, Yang Ming-Yu, Wang Feng, Qian Jin, Tang Hong, Chen Wan, He Gang, Shi You-xing, Yang Ai-Ning, Wang Yun-Jiao, He Yang, Mu Mi-Duo, Tao Xu, Li Yan |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Receptor
Platelet-Derived Growth Factor alpha Osteolysis Biophysics Bioengineering Exosomes Tendons Biomaterials Osteoclast microRNA Basic Helix-Loop-Helix Transcription Factors medicine Humans Chemistry Mesenchymal stem cell Scleraxis Mesenchymal Stem Cells medicine.disease Microvesicles MicroRNAs medicine.anatomical_structure Mechanics of Materials Drug delivery Ceramics and Composites Cancer research Nanocarriers |
| Zdroj: | Biomaterials. 279:121242 |
| ISSN: | 0142-9612 |
| DOI: | 10.1016/j.biomaterials.2021.121242 |
| Popis: | Osteolysis at the tendon-bone interface can impair pullout strength during tendon-bone healing and lead to surgery failure, but the effects of clinical treatments are not satisfactory. Mesenchymal stem cell (MSC)-derived exosomes have been used as potent and feasible natural nanocarriers for drug delivery and have been proven to enhance tendon-bone healing strength, indicating that MSC-derived exosomes could be a promising therapeutic strategy. In this study, we explored Scleraxis (Scx) dynamically expressed in PDGFRα(+) bone marrow-derived mesenchymal stem cells (BMMSCs) during natural tendon-bone healing. Then, we investigated the role of PDGFRα(+) BMMSCs in tendon-bone healing after Scx overexpression as well as the underlying mechanisms. Our data demonstrated that Scx-overexpressing PDGFRα(+) BMMSCs (BMMSCScx) could efficiently inhibit peritunnel osteolysis and enhance tendon-bone healing strength by preventing osteoclastogenesis in an exosomes-dependent manner. Exosomal RNA-seq revealed that the abundance of a novel miRNA, miR-6924-5p, was highest among miRNAs. miR-6924-5p could directly inhibit osteoclast formation by binding to the 3'-untranslated regions (3'UTRs) of OCSTAMP and CXCL12. Inhibition of miR-6924-5p expression reversed the prevention of osteoclastogenic differentiation by BMMSCScx derived exosomes (BMMSCScx-exos). Local injection of BMMSCScx-exos or miR-6924-5p dramatically reduced osteoclast formation and improved tendon-bone healing strength. Furthermore, delivery of miR-6924-5p efficiently inhibited the osteoclastogenesis of human monocytes. In brief, our study demonstrates that BMMSCScx-exos or miR-6924-5p could serve as a potential therapy for the treatment of osteolysis during tendon-bone healing and improve the outcome. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect