following molecules have been shown to play a crucial role in the production of healthy osteocytes, either in correct numbers or specific distributions: matrix metalloproteinases (MMPs), dentin matrix protein 1 (DMP-1), osteoblast/osteocyte factor 45 (OF45), Klotho, TGF-beta inducible factor (TIEG), lysophosphatidic acid (LPA), E11 antigen, and oxygen. 10–20% of osteoblasts differentiate into osteocytes. Those osteoblasts on the bone surface that are destined for burial as osteocytes slow down matrix production, and are buried by neighboring osteoblasts that continue to produce matrix actively. Palumbo et al. (1990) distinguish three cell types from osteoblast to mature osteocyte: type I preosteocyte (osteoblastic osteocyte), type II preosteocyte (osteoid osteocyte), and type III preosteocyte (partially surrounded by mineral matrix). The embedded "osteoid-osteocyte" must do two functions simultaneously: regulate mineralization and form connective dendritic processes, which requires cleavage of collagen and other matrix molecules. The transformation from motile osteoblast to entrapped osteocyte takes about three days, and during this time, the cell produces a volume of extracellular matrix three times its own cellular volume, which results in 70% volume reduction in the mature osteocyte cell body compared to the original osteoblast volume. The cell undergoes a dramatic transformation from a polygonal shape to a cell that extends dendrites toward the mineralizing front, followed by dendrites that extend to either the vascular space or bone surface. As the osteoblast transitions to an osteocyte, alkaline phosphatase is reduced, and casein kinase II is elevated, as is osteocalcin. Osteocytes appear to be enriched in proteins that are resistant to hypoxia, which appears to be due to their embedded location and restricted oxygen supply. Oxygen tension may regulate the differentiation of osteoblasts into osteocytes, and osteocyte hypoxia may play a role in disuse-mediated bone resorption. Function Although osteocytes are relatively inert cells, they are capable of molecular synthesis and modification, as well as transmission of signals over long distances, in a way similar to the nervous system. They are the most common cell type in bone (31,900 per cubic millimeter in bovine bone to 93,200 per cubic millimeter in rat bone). Most of the receptor activities that play an important role in bone function are present in the mature osteocyte. Osteocytes are an important regulator of bone mass. Osteocytes contain glutamate transporters that produce nerve growth factors after bone fracture, evidence of a sensing and information transfer system. When osteocytes were experimentally destroyed, the bones showed a significant increase in