The CAGS-Snorkel mouse: A game changer in the identification of extracellular vesicles originating from cells of the osteogenic lineage.

The production and deposition of vesicles within the matrix by growth plate chondrocytes were first described over 50 years ago in a series of elegant electron microscopy studies by Clarke Anderson and Ermanno Bonucci (1, 2). These matrix vesicles (MVs) are membrane limited and offer a sheltered interior to promote calcium phosphate precipitation and are now recognised to be critical for biomineralization of both bone and cartilage matrix. Since these pioneering days it has become abundantly clear that many other types of extracellular vesicles (EVs), of varying size, composition and origin, are produced by cells, including osteoblasts, osteocytes, osteoclasts and chondrocytes. EVs is a catch-all term for a heterogenous population of vesicles released by cells and this includes exosomes which are released from cells after the fusion of multivesicular bodies with the plasma membrane, and ectosomes/microvesicles that are derived from the outward budding of the plasma membrane (3).