Application and Molecular Mechanisms of Extracellular Vesicles Derived from Mesenchymal Stem Cells in Osteoporosis

Abstract

Osteoporosis (OP) is a chronic bone disease characterized by decreased bone mass, destroyed bone microstructure, and increased bone fragility. Accumulative evidence shows that extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) (MSC-EVs), especially exosomes (Exos), exhibit great potential in the treatment of OP. However, the research on MSC-EVs in the treatment of OP is still in the initial stage. The potential mechanism has not been fully clarified. Therefore, by reviewing the relevant literature of MSC-EVs and OP in recent years, we summarized the latest application of bone targeted MSC-EVs in the treatment of OP and further elaborated the potential mechanism of MSC-EVs in regulating bone formation, bone resorption, bone angiogenesis, and immune regulation through internal bioactive molecules to alleviate OP, providing a theoretical basis for the related research of MSC-EVs in the treatment of OP.

Exosomes as a potential therapeutic approach in osteoimmunology

“…Exosomes derived from tumor cells have been shown to activate osteoclastogenesis, explaining some mechanisms of osteoporosis onset in oncology (56)(57)(58)(59). Research data indicates that microRNAs such as miR-935, miR-21-5p, miR-27a-5p, miR-31a-5p, miR-29a, and miR-146a, which are encapsulated in exosomes in vivo, participate in bone tissue remodeling (60). Exosome-encapsulated miR-21a-5p was used in the design of an experimental bone implant and contributed to its osteointegration, as well as macrophage polarization towards the anti-inflammatory M2 phenotype, enhancing osteogenesis in a rat femoral bone drilling model (61).…”

Therapeutic potential of mesenchymal stem cell-derived exosomes in skeletal diseases

“…Perturbations in bone metabolism, such as an imbalance in the activities of osteoclasts (OCs) and osteoblasts (OBs), are also implicated in its pathogenesis. During recovery from OP, OBs secrete osteoids to facilitate bone regeneration ( Li et al, 2018 ; Yang et al, 2022 ). Currently available treatments (including anti-resorptive and anabolic drugs) control OP by promoting bone formation, impeding adipocyte development, or inhibiting OC differentiation.…”