Role of matrix vesicles in biomineralization

Abstract

Background: Matrix vesicles have been implicated in the mineralization of calcified cartilage, bone and dentin for more than 40 years. During this period, their exact role, if any in the nucleation of hydroxyapatite mineral, and its subsequent association with the collagen fibrils in the organic matrix has been debated and remains controversial.

Scope of review: This review summarizes studies spanning the whole history of matrix vesicles, but emphasizes recent findings and several hypotheses which have been recently introduced to explain in greater detail how matrix vesicles function in biomineralization.

Major conclusions: It is now generally accepted that matrix vesicles have some role(s) in mineralization; that they are the initial site of mineral formation; that MV bud from the plasma membrane of mineral forming cells, but that they take with them only a subset of the materials found in the parent membrane; that the three proteins, alkaline phosphatase, nucleotide pyrophosphatase phosphodiesterase and annexin V have important roles in the process and that matrix vesicles participate in regulating the concentration of PPi in the matrix. In contrast, many open questions remain to be answered.

General significance: Understanding the role of matrix vesicles in biomineralization will increase our knowledge of this important process.

Figure 1

Cross sectional model of early collagen mineralization. The open circles represent triple helical collagen molecules and the large hatched circles represent mineral within the hole zone channels.

Figure 2

Three possible mechanisms for the initiation of MV mediated matrix mineralization. In panel A, MV only regulate ion concentrations, leading to the formation of soluble molecular species which can initiate mineral formation in collagen fibrils. The circles represent MV, and the black lines depict mineral crystals. The double blue lines represent triple helical collagen molecules which are 300 nm in length. The dotted red line represents a dialysis membrane, which would not block mineralization by this mechanism. In panel B, MV regulate ion compositions leading to the formation of intravesicular apatite crystals, which leave the vesicle migrate to the mineralization front, where they seed collagen calcification. In panel C, MV associate directly with collagen, so that MV and matrix macromolecules cooperate to initiate matrix calcification.