Abstract

Bone is a complex organ maintained by three main cell types: osteoblasts, osteoclasts, and osteocytes. During bone formation, osteoblasts deposit a mineralized organic matrix. Evidence shows that bone cells release extracellular vesicles (EVs): nano-sized bilayer vesicles, which are involved in intercellular communication by delivering their cargoes through protein–ligand interactions or fusion to the plasma membrane of the recipient cell. Osteoblasts shed a subset of EVs known as matrix vesicles (MtVs), which contain phosphatases, calcium, and inorganic phosphate. These vesicles are believed to have a major role in matrix mineralization, and they feature bone-targeting and osteo-inductive properties. Understanding their contribution in bone formation and mineralization could help to target bone pathologies or bone regeneration using novel approaches such as stimulating MtV secretion in vivo, or the administration of in vitro or biomimetically produced MtVs. This review attempts to discuss the role of MtVs in biomineralization and their potential application for bone pathologies and bone regeneration.

Highlights

  • The matrix vesicles (MtVs) membrane contains a high concentration of PS, which can be detected with flow cytometry by binding to annexin A5 conjugated to a fluorescent probe [138]

  • MtVs are a subset of extracellular vesicles (EVs) that are secreted by, e.g., osteoblasts, chondrocytes, and odontoblasts, to directly induce mineralization of the organic matrix

  • Regardless of their biogenesis and heterogenicity, MtVs are all located in the extracellular matrix and all contribute to biomineralization through multiple mechanisms

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Bone is a multifunctional organ that is maintained through lifelong remodeling by the bone-forming osteoblasts, bone-resorbing osteoclasts, and the bone-regulating osteocytes These cells reside on/in a composite matrix, comprising mainly the organic collagen type 1 and the mineral hydroxyapatite which are highly organized at multiple hierarchical levels [1]. After mineral precursors have entered the collagen gap region, hydroxyapatite crystals grow outside the dimensions of the fibril, forming an interconnected continuous cross-fibrillar pattern [6] This mineralization is believed to be regulated by osteoblasts via indirect and direct mechanisms [7]. EVs are heterogenous in their size and morphology, and they can contain a variety of organic and inorganic cargoes such as lipids, proteins, genetic materials (DNA/RNA), and minerals derived from their parent cells [20,25,26,37]

Biogenesis of EVs
Plasma Membrane-Derived Ectosomes
Endosome-Originated Exosomes
Biological Potentials of EVs
Use of EVs in Diagnosis
Use of EVs for Therapy
EVs Derived from Bone Cells
MtVs and Their Contribution to Bone Mineralization
MtV Biogenesis and Characteristics
Ectosome-Like MtVs
Exosome-Like MtVs
ApoBDs Involved in Mineralization
Potential Collagen Mineralization Mechanisms
Isolation and Characterization of MtVs
Isolation of MtVs
Characterization of MtVs
Physical Properties
Biological Properties
Functional Properties
Therapeutic Potential of Osteoblast-Derived EVs and MtVs
Cellular Source of MtVs for Therapeutics
Potential Targets of MtVs for Bone Mineralization Disorders
Potential Risk of the Application of MtVs
Prospect for Therapeutic Applications of MtVs
Stimulation of MtV Secretion In Vitro and In Vivo
Chemical Stimuli for MtV Secretion
Physical Stimuli for MtV Secretion
Engineering Biomimetic MtVs
Proteoliposomes Mimicking MtVs
Polymeric Vesicles Mimicking MtVs
Findings
Conclusions

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