Degradation of Bone and the Role of Osteoclasts, Bone Lining Cells and Osteocytes - Extracellular Matrix Degradation - page 196

(Klein-Nulend et al. 1997 ). The different signaling molecules then modulate the
activity of cells at the bone surface. Formation of bone is modulated by PGE 2 and
sclerostin, NO inhibits the activity of osteoclasts. The latter cells are attracted to the
resorption site by signals sent by apoptotic osteocytes (Bronckers et al. 1996 ;
Burger et al. 2003 ; Gu et al. 2005 ). Also a direct cell-cell contact between osteocyte
extensions and the bone lining cells occurs and probably results in a localized
activation of the bone lining cell to attract the osteoclast precursor.

8.2.1.2 Chemokines Attract the Mononuclear Osteoclast Precursors

The bone lining cells secrete chemokines, like CCl9, that attract mononuclear
precursors of osteoclasts (Yu et al. 2004 ). The release of the chemokines
probably results in the activation of the endothelial cells of blood vessels in the
near vicinity of the bone surface. The activated endothelial cells then attract the
mononuclear cells (e.g., monocytes) that are primed to become osteoclasts. These
monocytes leave the blood vessel and migrate towards and attach to the bone
lining cell.

8.2.2 The Generation of Osteoclasts and the Role
of the Bone Lining Cell

8.2.2.1 Interaction of the Precursor with the Bone Lining

Cell Induces Essential Modifications

The attachment of the mononuclear osteoclast precursor is mediated by intercellu-
lar cell-associated molecule 1 (ICAM-1) expressed by the bone lining cell and
leukocyte function-associated protein 1 (LFA-1) present on the membrane of
the mononuclear cell (Gao et al. 2000 ; Kurachi et al. 1993 ; Tanaka et al. 1995 ;
Bloemen et al. 2009 ). Following this attachment, the interaction between the two
cell types results in significant changes in gene expression of each cell type. The
expression of genes associated with attachment, like ICAM-1, increases synergisti-
cally (Bloemen et al. 2010 ). A similar phenomenon is also found for the expression
of genes responsible for the formation of the multinucleated osteoclasts, RANK,
RANKL and M-CSF. In the mean time OPG is strongly upregulated. Together these
findings suggest that an efficient osteoclastogenesis occurs when the cell is in direct
contact with the bone lining cell. In the mean time a high level of OPG prevents
formation at sites where such a close cell-cell relationship does not occur. This
cell-cell interaction eventually results in the formation of tartrate-resistant acid
phosphatase (TRACP) positive mononuclear osteoclasts (Perez-Amodio et al.
2004 ).