From their ends adjacent to the matrix, osteoblasts secrete type I collagen, several glycoproteins, and proteoglycans. Some of these factors, notably osteocalcin and certain glycoproteins, bind Ca2+ with high affinity, thus raising the local concentration of these ions. Osteoblasts also release very small membrane-enclosed matrix vesicles with which alkaline phosphatase and other enzymes are associated. These enzymes hydrolyze PO4− ions from various macromolecules, creating a high concentration of these ions locally. The high ion concentrations cause calcified nanocrystals to form in and around the matrix vesicles. The crystals grow and mineralize further with formation of small growing masses of calcium hydroxyapatite [Ca10(PO4)6(OH)2], which surround the collagen fibers and all other macromolecules. Eventually the masses of hydroxyapatite merge as a confluent solid bony matrix as calcification of the matrix is completed.