Biology Reference
In-Depth Information
ICAM-1
Intercellular-associated molecule 1
IL-1, -6
Interleukin-1, -6
LAMP-2
Lysosome-associated membrane protein 2
LFA-1
Leukocyte function-associated protein 1
M-CSF
Monocyte colony stimulating factor
MMP
Matrix metalloproteinase
NFAT
Nuclear factor of activated T cells
NHA2
Sodium-proton antiporter 2
NO
Nitric oxide
OPG
Osteoprotegerin
PA (tPA, uPA)
Plasminogen activator (tissue, urokinase)
PEDF
Pigment epithelium derived factor
PGE
2
Prostaglandin E
2
PTH
Parathyroid hormone
RANK(L)
Receptor activator nuclear kappa (ligand)
ROS
Reactive oxygen species
SlC4a4
Solute carrier 4a4
Spp24
Secreted phosphoprotein 24
TGF
Transforming growth factor
b
b
TNF
Tumour necrosis factor
a
a
TRACP
Tartrate-resistant acid phosphatase
V-ATPase
Vacuolar ATPase
8.1
Introduction
Bone is a unique tissue since it not only consists of extracellular matrix constituents
like collagen, but also contains high levels of the mineral hydroxyapatite. Degrada-
tion of bone requires therefore cells that have the capacity to digest both mineral
and collagen. The multinucleated osteoclasts are equipped for this task. These cells
are generated locally at the site where resorption has to occur, a process organized
and modulated by osteoblast-like cells, the bone lining cells. Mononuclear osteo-
clast precursors are attracted by the bone lining cells, attach to these cells and due to
the interaction with the bone lining cells, transform into osteoclasts. In the mean
time the bone lining cells clean the mineralized bone surface from non-mineralized
collagen fibrils thus paving way for the osteoclast to attach to the bone. The
osteoclast firmly adheres to the bone surface and isolates an area of this surface
from the rest of the extracellular environment. In this secluded area the actual
resorption takes place. First, the pH is lowered due to the release of H
+
by proton
pumps present in the resorption membrane. The lower pH results in dissolution of
the mineral component of the bone. Next, proteolytic enzymes are secreted in the
resorption area. These proteolytic enzymes, of which cathepsin K is one of the most
