Matrix vesicles: Are they anchored exosomes?

Abstract

Numerous studies have documented that matrix vesicles are unique extracellular membrane-bound microparticles that serve as initial sites for mineral formation in the growth plate and most other vertebrate mineralizing tissues. Microparticle generation is not confined to hard tissues, as cells in soft tissues generate similar structures; numerous studies have shown that a common type of extracellular particle, termed an exosome, a product of the endosomal pathway, shares many characteristics of matrix vesicles. Indeed, analyses of size, morphology and lipid and protein content indicate that matrix vesicles and exosomes are homologous structures. Such a possibility impacts our understanding of the biogenesis, processing and function of matrix vesicles (exosomes) in vertebrate hard tissues and explains in part how cells control the earliest stages of mineral deposition. Moreover, since exosomes influence a spectrum of functions, including cell-cell communication, it is suggested that this type of microparticle may provide a mechanism for the transfer of signaling molecules between cells within the growth plate and thereby regulate endochondral bone development and formation.

Keywords: Chondrocyte; Exosome; Growth plate; Matrix vesicle; Mineralization; Osteoblast.

Figure 1

Transmission electron micrographs of matrix vesicles in the rat growth plate. Early mineralization of a vesicle is observed as an accumulation of electron dense material in the vesicle membrane (A, arrowheads) and in the vesicle interior (B). Scale bar = 50 nm. Images used with permission from Amizuka et al. [74].

Figure 2

Transmission electron micrograph of the leg tendon from a normal 15-week-old turkey. Tissue was fixed in 2.5% glutaraldehyde-1% paraformaldehyde overnight at room temperature, embedded in epoxy, sectioned and stained with uranyl acetate-lead citrate. Matrix vesicles of various sizes are found disposed between parallel arrays of type I collagen fibrils. Vesicles, stained for alkaline phosphatase, exhibit an enhanced electron density. Scale bar = 1 µm.

Figure 3

Transmission electron micrographs of osteoblast-like cells showing aggregated vesicles close to the plasma membrane and enclosed in sacs (a–c). Images used with permission from Xiao et al. [75].

Figure 4

Schematic diagram of pathways for formation of mineralizing exosomes (matrix vesicles). The classical endosomal pathway exhibited by almost all cells of the body requires that protein molecules (blue) are taken into target cells by receptor-mediated endocytosis and form early endosomes. In the presence of ubiquitin (light blue crosses), ESCRT proteins (dark blue shafts), and early endosomes, multivesicular bodies are formed. The multivesicular bodies can also receive molecular cargo from autophagosomes. Multivesicular bodies may fuse with regions of the plasma membrane rich in raft lipids and proteins and release their accumulated microparticles to the outside of the cell as mineralizing exosomes. Very recent studies suggest that autophagosomes may contain mineral nuclei (white particles in the autophagosome). Autophagosomes may transport such nuclei to the plasma membrane and release them from the cell as mineralizing exosomes or blebs of mineralizing ectosomes. Multivesicular bodies and early endosomes can form amphisomes which can fuse with lysosomes to form autophagolysosomes. Multivesicular bodies and late endosomes may also form autophagolysosomes. Autophagolysosomes can degrade their cargo which is then recycled.