Early mineralization of matrix vesicles in the epiphyseal growth plate

Abstract

Matrix vesicles (MVs) induce the primary mineralization in collagen-rich hard tissues such as bone, mineralizing cartilage and dentine. Calcium and phosphate ions accumulate at the inner MV membrane. This accumulation takes place in association with phospholipids alone and/or in association with Annexin V, which displays Ca ion channel activity when inserted in membranes; consequently, Annexin V may be involved in Ca uptake by matrix vesicles. The first crystal nuclei are formed at these macromolecules of the MV inner membrane. They grow to stable nanometre-sized particles, dots, which coalesce to form chains of dots along the macromolecules of the MV inner membrane. At the same time, or shortly afterwards, chains of these Ca phosphate dots also develop inside the MVs. The measured centre-to-centre distances between these dots represent approximately the distances between the nucleating sites, called active sites, along the MV matrix molecules. The mineralization does not stop at the MV membrane but expands continuously into the extravesicular region in radial directions to form nodules. These radiating Ca phosphate chains, which coalesce to form needles, are composed of such primary dots, which have developed at the nucleating sites of the corresponding macromolecules.

Cell-Mediated Crystallization of Calcium Oxalate in Plants

“…High-resolution ultrastructural studies have shown that center-to-center distances between particles in the inner face of matrix vesicle membranes are consistent with calcium phosphate nucleation (Plate et al, 1996). Isolated matrix vesicles also promote mineralization in vitro (Boskey et al, 1997).…”

Intracellular precipitation of hydroxyapatite mineral and implications for pathologic calcification

“…Likewise, a similar layered structure has also been observed in clay minerals in an exclusively inorganic system without cells or proteins (Vali and Bachmann, 1988;Vali et al, 2001). A multi-step mineralization pattern for hydroxyapatite formation has also been reported during the initial mineralization events in matrix vesicles found in cartilage extracellular matrix (Kirsch et al, 1997;Plate et al, 1996).…”

“…Other challenges are to understand the atomic-level chemistry that occurs within the calcifying vesicles that results in the deposition of the very first crystals, and whether this process is inorganically driven or derives at least initially from the loss of potent mineralization inhibitors such as pyrophosphate and fetuin-A. While the mode of mineralization in matrix vesicles and their role in both physiologic and ectopic calcification have been studied extensively (Anderson, 1969(Anderson, , 1990Anderson et al, 2004;Bonucci, 1970;Hsu and Anderson, 1978;Kirsch et al, 1997;Plate et al, 1996), there is little data available on the intracellular process we describe here. While needing further study, we propose that calcification specifically associated with intracellular, membrane-bounded organelles triggered by dysregulated cell processes represents an additional mechanism for inducing ectopic calcification.…”

New biomineralization strategies for the use of natural-based polymeric materials in bone-tissue engineering

“…In hard tissues, such as bone and mantle dentin, it is generally accepted that the mineralization process starts within extracellular-bond structures known as matrix vesicles (MV) (Anderson, 1967;Bonucci, 1967;Boskey, 1999b;Kirsch, et al, 1997b;Plate, et al, 1996;Wiesmann, et al, 2005). These MV are the result of a polarized budding process that occurs in osteoblasts, odontoblasts and in chondrocytes present in the epiphyseal growth plate, a region where longitudinal bone growth occurs.…”

“…The uptake of calcium ions is parallel to the inward movement of phosphorous ions, which occurs via the activation of sodium-dependent phosphate transporters. According to some studies, the phosphatidylserine first binds to calcium ions to form a calcium-phospholipid-phosphate complex (Anderson, 1967;Bonucci, 1967;Plate, et al, 1996). This binding with calcium ions, and phosphate ions, induces the formation of nucleation regions (Morris, et al, 1992;Plate, et al, 1996).…”