Matrix Vesicle-Mediated Mineralization and Osteocytic Regulation of Bone Mineralization

Abstract

Bone mineralization entails two mineralization phases: primary and secondary mineralization. Primary mineralization is achieved when matrix vesicles are secreted by osteoblasts, and thereafter, bone mineral density gradually increases during secondary mineralization. Nearby extracellular phosphate ions (PO43−) flow into the vesicles via membrane transporters and enzymes located on the vesicles’ membranes, while calcium ions (Ca2+), abundant in the tissue fluid, are also transported into the vesicles. The accumulation of Ca2+ and PO43− in the matrix vesicles induces crystal nucleation and growth. The calcium phosphate crystals grow radially within the vesicle, penetrate the vesicle’s membrane, and continue to grow outside the vesicle, ultimately forming mineralized nodules. The mineralized nodules then attach to collagen fibrils, mineralizing them from the contact sites (i.e., collagen mineralization). Afterward, the bone mineral density gradually increases during the secondary mineralization process. The mechanisms of this phenomenon remain unclear, but osteocytes may play a key role; it is assumed that osteocytes enable the transport of Ca2+ and PO43− through the canaliculi of the osteocyte network, as well as regulate the mineralization of the surrounding bone matrix via the Phex/SIBLINGs axis. Thus, bone mineralization is biologically regulated by osteoblasts and osteocytes.

Concentration-Dependent Efficacy of Recombinant Human Bone Morphogenetic Protein-2 Using a HA/β-TCP Hydrogel Carrier in a Mini-Pig Vertebral Oblique Lateral Interbody Fusion Model

“…This occurs as Ca 2+ binds strongly to the inner leaflet of the plasma membrane, which is generally negatively charged, and binds strongly to phosphatidylcholine and phosphatidylserine in the leaflet [36,37]. HA crystals are then formed, which penetrate the plasma membrane to give rise to mineralized nodules [38]. The mineralization of the collagen deposition of calcium phosphate begins from the mineralized nodules that are produced, forming and completing grains [39].…”

Biocompatibility Evaluation of Carbon Nanohorns in Bone Tissues

“…Furthermore, in vivo bone tissue specimens confirmed that some CNHs were present in the bone matrix and within the lacunae. Moreover, CNHs resemble the shape of calcified vesicles [ 25 ]. These results suggest that OBs may have recognized CNHs as resembling the shape of calcified vesicles, incorporated them into the cells, and thus increased the number of calcified vesicles.…”

Advances in Multifunctional Bioactive Coatings for Metallic Bone Implants

“…Further mineral accumulation in the MV is achieved through ion channels and transporters leading to initial nucleation and calcification in the MV. Finally, needle-like hydroxyapatite crystals are released from the MV into the extravesicular fluid, these crystals subsequently being incorporated into the collagen fibril network [14,15]. Some osteoblasts become incorporated into the matrix and turn into immature osteocytes embedded in the fully mineralized and matured matrix [16,17].…”