Biology Reference
In-Depth Information
transported through the cytoplasm to the opposite part of the cell (Salo et al.
1997
),
the functional secretory domain ((Mulari et al.
2003b
), FSD; Fig.
8.3
). The parts of
the ruffled border that surround the endocytic central part are primarily involved in
secretion of enzymes needed for resorption (Mulari et al.
2003a
).
8.2.5 Lowering of the pH Results in Dissolution of Mineral
8.2.5.1 Role of Different Membrane Pumps in the Ruffled Border
Lowering of the pH depends on the presence of specialized pumps in the ruffled
border membrane. The V-ATPase is the membrane-bound pump that releases H
+
into the extracellular space. The proton is derived form carbonic acid which is
converted by carbonic anhydrase II into bicarbonate and H
+
. To achieve electro-
neutrality, a chloride channel (ClC7) transports Cl
into the extracellular area
facing the ruffled border. Also ClC7 is localized in the membrane of the ruffled
border (Hall and Chambers
1989
; Karsdal et al.
2005
; Kornak et al.
2001
). Each of
the three molecules mentioned, V-ATPase, carbonic anhydrase II and ClC7, have
been shown to be crucial for the proper functioning of the osteoclast and thus for the
degradation of bone. In the absence of each of these proteins the osteoclast can no
longer degrade the bone, resulting in osteopetrosis (Helfrich
2003
). Under these
conditions osteoclasts are formed in normal or even higher numbers, they attach to
the bone, but they do not form a ruffled border which is essential for the resorption
to occur (Fig.
8.4
).
8.2.5.2 Role of Pumps Localized in the Baso-Lateral Membrane
Secretion of H
+
and the presence of increased levels of bicarbonate severely
influence the intracellular pH. To create a physiological
intracellular pH,
OC
OC
OC
OC
OC
Fig. 8.4 Light micrograph of
a bone biopsy of a patient
suffering from osteopetrosis.
Note the large number of
osteoclasts (OC) but absence
of active resorption by these
cells [From Everts et al.
(
2009
).]
OC
OC
OC
