Extracellular Vesicles in Gut-Bone Axis: Novel Insights and Therapeutic Opportunities for Osteoporosis.

Osteoporosis (OP) is a systemic and retrogressive disease characterized by decreased bone density and fragile bone microstructure. Extracellular vesicles (EVs), a cell-free system with a phospholipid bilayer released by cells that cannot be replicated, have unique nanostructure, stable drug-loading capacity, and good biocompatibility, playing an important role in regulating the gut-skeletal axis. A growing body of research demonstrates that gut microbiota (GM) influence the development of OS, while bacteria-derived EVs (BEVs) have become a new dialogue medium between the gut and bone. Additionally, organoids are 3D cell clusters in vitro that highly simulate the structure and function of corresponding organs. Intestinal organoids-derived EVs (IOEVs) serve as another promising communication medium between the gut and bone due to their significant physiological effects. Herein, three types of gut-bone axes, including the traditional, BEVs-based, and IOEVs-based gut-bone axes are innovatively proposed. The impact of the BEVs-based and IOEVs-based gut-bone axes on OP is focused. The comprehensive summary of three types of gut-bone axes will reveal the relationship between intestinal and bone and provide new solution to OP therapy.