Osteocytes are derived from Osteoblasts. The fossil record shows that osteocytes were present in bones of jawless fish 400-250 million years ago, and dinosaurs 80 million years old. Therefore, osteocytes have been used to estimate the size of the genome of extinct species.
During bone formation, an osteoblast is left behind and buried in the bone matrix as an "osteoid osteocyte", which maintains contact with the osteoblasts through extending cellular processes. The process of osteocytogenesis is largely unknown, but the 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 gene, TGF Beta inducile factor (TIEG), Lysophosphatidic acid (LPA), E11 antigen, and Oxygen. The transformation from motile osteoblast to entraped 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. 10-20% of osteoblasts differentiate into osteocytes. 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. 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. As the osteoblast transitions to an osteocyte, alkaline phosphatase is reduced, and casein kinase II is elevated, as is osteocalcin. 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.
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.
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