Matrix Vesicle-Mediated Mineralization and Osteocytic Regulation of Bone Mineralization

• Published in: International journal of molecular sciences Vol. 23; no. 17; p. 9941
• Main Authors: Hasegawa, Tomoka, Hongo, Hiromi, Yamamoto, Tomomaya, Abe, Miki, Yoshino, Hirona, Haraguchi-Kitakamae, Mai, Ishizu, Hotaka, Shimizu, Tomohiro, Iwasaki, Norimasa, Amizuka, Norio
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.09.2022; MDPI
• Subjects: Binding sites; Bone matrix; Bone mineral density; bone mineralization; Calcium ions; Calcium phosphates; Calcium transport; Collagen; Crystal growth; Crystals; Enzymes; Fibrils; Hydroxyapatite; Kinases; matrix vesicle; Matrix vesicles; Membrane vesicles; Membranes; Mineralization; Nodules; osteoblast; Osteoblasts; osteocyte; Osteocytes; Phex/SIBLING; Phosphate esters; Plasma; Proteins; Review; Vesicles
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23179941

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.