Osteocyte apoptosis

Abstract

Apoptotic death of osteocytes was recognized over 15 years ago, but its significance for bone homeostasis has remained elusive. A new paradigm has emerged that invokes osteocyte apoptosis as a critical event in the recruitment of osteoclasts to a specific site in response to skeletal unloading, fatigue damage, estrogen deficiency and perhaps in other states where bone must be removed. This is accomplished by yet to be defined signals emanating from dying osteocytes, which stimulate neighboring viable osteocytes to produce osteoclastogenic cytokines. The osteocyte apoptosis caused by chronic glucocorticoid administration does not increase osteoclasts; however, it does negatively impact maintenance of bone hydration, vascularity, and strength.

Figure 1

Morphology of apoptotic osteocytes. a. Brightfield image of osteocyte lacuna in human infant calvarial bone containing a cell with condensed chromatin (arrowhead) and spherical structures resembling apoptotic bodies (arrows). b. Scanning electron microscope (SEM) image of apoptotic osteocyte-like MLO-Y4 cells demonstrating extensive blebbing (arrowhead) which will become apoptotic bodies (arrows). c. SEM image of necrotic swollen MLO-Y4 cell with ruptured cell membrane, which contrasts with the cell shrinkage seen in apoptotic cells. d. Active caspase-3 immunostaining (brown) in osteocytes near sites of microdamage in mouse bone. Viable osteocytes are blue. Image provided courtesy of O. Kennedy, Ph.D. and M.B. Schaffler, Ph.D. of the City College of New York.

Figure 2

ISEL-labeled (brown) apoptotic osteocytes with condensed nuclei are plentiful in murine vertebral cortical bone after 28 days of prednisone administration.

Figure 3

Abundant apoptotic osteocytes (TUNEL) (long arrows) and lining cells (short arrows) are present in sections of human whole femoral heads obtained during total hip replacement for glucocorticoid-induced osteonecrosis. Empty osteocytic lacunae are rare.