Proteoglycans and Biomineralization of Bone and Dentin

Although many advances have been made during the last six decades, the controlled processes by which vertebrate hard tissues acquire, organize, and maintain their mineral component remain only partially understood. Mineralized tissues can be classified into two categories based on their developmental origin. Enamel is the only hard tissue of epithelial origin; all other hard tissues are of connective tissue origin and therefore possess a collagen-rich extracellular matrix as their main organic component. The cells responsible for the formation of collagen-based hard tissues regulate the synthesis and degradation of non-collagenous components, among which proteoglycans (PGs) play a key role in biomineralization. This review focuses on the mineralization process of bone and dentin, highlighting the highly coordinated sequential events leading to the acquisition of the mineral phase. Initially, the forming cells release numerous small spherical membrane-limited bodies known as matrix vesicles (MVs), which constitute the nanocompartments necessary for the onset of mineral nucleation (vesicular stage). At this stage, extracellular matrix PGs bind to the MV membrane and subsequently to calcium ions, thereby allowing the accumulation of high concentrations of calcium around the MVs. Following PG degradation, calcium ions enter the MVs through annexin channels, leading to the nucleation and growth of the first mineral crystals. Subsequently, cells orchestrate the conditions required for mineral propagation into the surrounding collagenous matrix (fibrillar stage). During this phase, PGs and other non-collagenous matrix components play a crucial role in promoting mineralization progression as well as in limiting and interrupting the process.