Coupling of Intracellular Calcium Homeostasis and Formation and Secretion of Matrix Vesicles: Their Role in the Mechanism of Biomineralization.

The human bone is a dynamic, highly vascularized tissue composed of 60-70% minerals, which include mainly calcium phosphate (CaP) in the form of hydroxyapatite (HA) crystals, 30% organic matrix composed of type I collagen fibers, and less than 5% water and lipids. The crystals are formed inside the matrix vesicles (MVs) and are then released in the organic collagen-based fibrous matrix. Extracellular matrix (ECM) formation and mineralization processes, named osteogenesis, are associated with human mesenchymal stem cells (hMSCs) undergoing differentiation into osteoblasts (osteoblastogenesis). Osteogenesis is regulated by multiple intracellular signaling and genetic pathways and by environmental factors. Calcium flow is finely regulated and plays a key role in both osteoblastogenesis and osteogenesis. The formation and accumulation of CaP, the biogenesis of MVs, their secretion, and the deposition of HA crystals to fill the organic bone matrix are the fundamental events in the biomineralization process. In this paper, I will describe and discuss the recent findings and hypothesis on the molecular mechanism regulating this process.