Exosomes Derived from Adipose Stem Cells Enhance Bone Fracture Healing via the Activation of the Wnt3a/β-Catenin Signaling Pathway in Rats with Type 2 Diabetes Mellitus

Abstract

Nonunion and delayed union are common complications of diabetes mellitus that pose a serious health threat to people. There are many approaches that have been used to improve bone fracture healing. Recently, exosomes have been regarded as promising medical biomaterials for improving fracture healing. However, whether exosomes derived from adipose stem cells can promote bone fracture healing in diabetes mellitus remains unclear. In this study, adipose stem cells (ASCs) and exosomes derived from adipose stem cells (ASCs-exos) are isolated and identified. Additionally, we evaluate the in vitro and in vivo effects of ASCs-exos on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and bone repair and the regeneration in a rat model of nonunion via Western blotting, immunofluorescence assay, ALP staining, alizarin red staining, radiographic examination and histological analysis. Compared with controls, ASCs-exos promoted BMSC osteogenic differentiation. Additionally, the results of Western blotting, radiographic examination and histological analysis show that ASCs-exos improve the ability for fracture repair in the rat model of nonunion bone fracture healing. Moreover, our results further proved that ASCs-exos play a role in activating the Wnt3a/β-catenin signaling pathway, which facilitates the osteogenic differentiation of BMSCs. All these results show that ASCs-exos enhance the osteogenic potential of BMSCs by activating the Wnt/β-catenin signaling pathway, and also facilitate the ability for bone repair and regeneration in vivo, which provides a novel direction for fracture nonunion in diabetes mellitus treatment.