Biology Reference
In-Depth Information
Fig. 8.1 A bone lining cell
engulfs non-mineralized
collagen fibrils protruding
from the bone surface and
cleans this surface prior to
osteoclastic bone degradation
at that site
bone lining cell
on bone surface
bone
engulfment
of collagen fibrils
MMP-13 (Behonick et al.
2007
; Inada et al.
2004
) and/or MMP-14 (Andersen et al.
2004
) herein.
The removal and degradation of the collagen fibrils probably results in the
release of small fragments. Since Holliday et al. (
1997
) and more recently Eck
et al. (
2009
) demonstrated that MMP-1 and the fragments of type I collagen
generated by the activity of this enzyme had an activating and differentiating effect
on osteoclasts and their precursors, it is tempting to suggest that such a process
occurs on the bone surface and is mediated by the action of the bone lining cells.
8.2.4 Attachment of the Osteoclast to the Bone Surface
8.2.4.1 Formation of Sealing Zone and Ruffled Border
Attachment of the osteoclast to the bone surface depends on the presence of the
integrin
a
v
b
3
, which is highly expressed by these cells (Helfrich et al.
1996
;
Lakkakorpi et al.
1991
) (Fig.
8.2
). The integrin attaches to proteins like osteopontin
(Horton et al.
1995
), a protein abundantly present in bone. The moment the
osteoclast is attached to the bone, the cell starts expressing some unique properties.
The cell becomes highly polarized and forms first the so-called sealing zone, an
area characterized by a high density of actin filaments and attachment sites. This
zone more or less creates in its centre an area adjacent to the osteoclast that is
secluded from the rest of the extracellular environment. The central area thus
created is characterized by deeply indented membrane folds and is called the ruffled
border (Fig.
8.3
). This membrane is formed by fusion of lysosomal vacuoles with
the outer membrane and is considered a secondary lysosome. Proteins characteris-
tic for the lysosomal membrane are highly expressed in this membrane, e.g.,
Lysosome-associated membrane protein 1 (LAMP-1), LAMP-2 and V-ATPase
(reviewed in (Everts and Beertsen
2005
)).
Adjacent to this membrane the actual resorption takes place, first by lowering the
extracellular pH and then by secreting proteolytic enzymes in this area. Studies by
