Taking a closer look at matrix vesicle biogenesis.

Matrix vesicles (MVs) are crucial components in the development of a healthy mineralized skeleton. They are also the key elements leading to the pathological calcification of vasculature; however, we know surprisingly little about them. First characterized over 55 yr ago, MVs are small membrane bound extracellular vesicles (EVs) that provide an environment for the concentration of calcium and phosphate. This makes MVs the first step in producing calcium phosphate, leading to the nucleation of HA mineral within the extracellular matrix, the key process in biomineralization. In this review, we discuss the literature on MV biogenesis and explore their components in the context of EVs and exosomes. We consider MVs in light of the Minimal Information for Studies of Extracellular Vesicles (MISEV2023). In doing so, we identify striking parallels in the biogenesis, contents, and roles of MVs and exosomes, opening opportunities for new avenues of research and understanding. We also explore the debate around whether MVs really contain HA, and propose emerging technologies, particularly in the field of imaging, to improve our understanding of MVs and galvanize research in the area over the coming years. By taking a closer look at MV biogenesis, we will be able to make use of the emerging technologies around EVs more widely, with the aim of fully understanding these vital vesicles and harnessing their potential therapeutic benefits.