Bone-Targeting HUVEC-Derived Exosomes Containing miR-503-5p for Osteoporosis Therapy

Abstract

Osteoporosis (OP) is a systemic bone disease characterized by decreased bone mass, damaged bone microstructure, increased bone fragility, and increased risk of fractures. It is more common in postmenopausal women and elderly people. The development of drugs with a high bone-targeting ability is urgently needed. We prepared a bioactive nanoparticle that modified the exosomes derived from human umbilical vein endothelial cells (HUVEC-Exo miR-503-high ) to contain a large amount of miR-503-5p, with a diameter range of 30−150 nm. The HUVEC-Exo miR-503-high that we constructed had the same characteristics as ordinary exosomes and could bind to osteoblasts/ osteoclasts in vitro. Moreover, they exhibited better bone-targeting ability than exosomes derived from other sources of bone marrow stromal cells in vivo. Bioinformatics analysis showed that miR-503-5p is strongly associated with bone-related pathways. In vitro experiments showed that HUVEC-Exo miR-503-high effectively inhibited osteoclast differentiation and promoted osteogenic differentiation. In vivo experiments showed that injecting HUVEC-Exo miR-503-high into OP mice significantly increased bone density and prevented OP. HUVEC-Exo miR-503-high can be used for bone-targeted therapy of OP, providing an approach to the clinical prevention and treatment of OP.

Advances in non-coding RNA in tendon injuries

“…It is promising that the spectrum of noncoding RNAs in tendinopathies and the role of individual noncoding RNAs in tendon repair and healing are being progressively uncovered. Non-coding RNA-based strategies have shown considerable beneficial effects on improving tendon healing in terms of reducing adhesions, promoting remodeling, and facilitating angiogenesis (Zhang et al, 2022;J et al, 2021;Huang et al, 2024;Luo et al, 2022). Although non-coding RNA therapies for tendon repair have shown promise, there are challenges in translating these therapies into clinical application.…”