Degradation of Bone and the Role of Osteoclasts, Bone Lining Cells and Osteocytes - Extracellular Matrix Degradation - page 201

Fig. 8.5 Immunolocalization
of anion exchanger 2 (Ae2) in
the baso-lateral membrane of
a mouse osteoclast. Note the
high level of staining
exclusively present in the
baso-lateral membrane. The
resorption zone (RB) is
devoid of the exchanger
(Micrograph donated by
Bronckers, ACTA,
Amsterdam, The
Netherlands.)

osteoclast

RB

bone

bicarbonate has to be extruded from the cell and in the mean time Cl has to be
transported into the cell. For this activity an anion exchanger (AE) is necessary.
Recent findings indicate that of the four known anion exchangers, AE2 is the one
used by the osteoclast for this activity (Josephsen et al. 2009 ; Wu et al. 2008 ; Jansen
et al. 2009 ). The exchanger is localized in the baso-lateral membrane of the
osteoclast (Fig. 8.5 ), and in its absence, the osteoclast does not form a ruffled
border (Jansen et al. 2009 ), a phenomenon also seen with the other pH-modulating
proteins as mentioned in 8.2.5.1.
Of considerable interest is the finding that in mice, osteoclasts at different bone
sites appear to differ with respect to the exchanger they use. Osteoclasts that
harbour long bones depend solely on Ae2 a,b , whereas those present in the skull
use next to this exchanger also the sodium transporter SlC4a4 (Jansen et al. 2009 ).
The differences among osteoclast subpopulations will be discussed in more detail
below (see Sect. 8.2.6.5 ).

8.2.5.3 Effect of pH Changes on Osteoclastic Activity

Slight changes in the pH of the environment greatly affects the activity of osteo-
clasts (Arnett 2003 , 2008 ). A lower pH simulates resorption significantly. Muzylak
et al. ( 2007 ) found that a relatively small decrease in pH, from pH 7.25 to 7.15,
resulted in a highly significant increase in the size of the osteoclasts. Under these
conditions osteoclasts were eight times larger and contained more nuclei. Others
have shown that the level of resorption is related to the size of the osteoclast; the
larger the osteoclast is, the more bone is resorbed (Hu et al. 2008 ; Lees et al. 2001 ).
So, it appears that the size of the osteoclast and thus the fusion of mononuclear
precursors are modulated by the pH. Somehow the cell senses changes in pH and
these changes highly influence the osteoclast formation and subsequent bone
degradation.