Chapter 10 Chapter 10 Osteocytes Copyright © 2013 Elsevier Inc. All rights reserved.

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Chapter 10 Chapter 10 Osteocytes Copyright © 2013 Elsevier Inc. All rights reserved.

FIGURE 10.1 Procion red staining of the osteocye lacuno-canalicular system in mouse cortical bone. Note the complexity of the network and the orderly alignment of lacunae. Source: figure provided by Dr. Jian Feng, University of Missouri-Kansas City. 2

Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 10.2 Osteoblast to osteocyte ontogeny. This diagram represents the process of differentiation from osteoblast precursors to matrix-producing cells, to cells embedded in osteoid, to cells embedded in the mineralized matrix. The markers listed below are relative and overlapping. E11 is the earliest marker specific for the embedding osteocyte [26,28]. There appears to be some early expression of Dmp1 and Phex in osteoblasts, but the greatest expression is found in osteocytes [36,37,41]. The expression of sclerostin or Sost in osteocytes appears delayed compared to other markers for osteocytes [54]. 3

Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 10.3 Osteocytes make contact with cells on the bone surface. The image is an acid-etched resin embedded murine bone visualized by scanning electron microscopy showing the high interconnectivity of the osteocyte lacuna-canalicular system. The top figure shows the resin- embedded marrow on the top and the complex osteocyte lacuno-canalicular network below where the mineral has been removed by acid etching. The bottom figure is a magnification showing canaliculi in contact with the bottom of a cell on the surface of the bone (arrow). 4

Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 10.4 Canaliculi, dendrites, and fluid flow: it has been proposed that molecules travel in the bone fluid through a glycocalyx which surrounds the dendritic processes within the caniluculi [303]. The dendritic process appears to be anchored to the wall of the canaliculi by integrins [144]. The glycocalyx acts as a sieve or “fishnet” to allow molecules below a size of approximately 7 nm to pass [304]. Studies suggest that molecules as large as albumin can pass through the canaliculi and that the bone fluid serves to provide nutrients to the osteocyte. It has been proposed that immobilization causes a lack of bone fluid flow which in turn causes hypoxia, followed by osteocyte cell death [305]. Fluid flow-induced prostaglandin (PG)E2 release by MLO-Y4 cells is reduced by the degradation of the glycocalyx on the cell surface, a hypothesized mechanosensor in osteocytes [306]. Clearly the dendritic processes of osteocytes serve numerous functions. 5

Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 10.5 The effects of lacuno-canalicular system complexity on bone mass or health is not known. Complexity may increase with age of the animal. Disruptions to this system may occur with disease [279]. Theoretically, changes in osteocyte dendricity would have a dramatic effect on osteocyte function and viability and on the mechanical properties of bone. 6