Biomedical Engineering Reference
In-Depth Information
Osteoclasts
Osteoblasts
Figure 1.24
Osteoblasts and osteoclasts on trabecula of lower jaw of calf embryo. After
[63].
expressed on dendritic cells and facilitates immune signaling. RANKL is found
on the surface of stromal cells, osteoblasts, and T cells. RANK is expressed on
osteoclasts, T lymphocytes, and dendritic cells, and its ligation with RANKL leads
to cellular activation. However, another member of the TNFR family, OPG, acts as
a decoy receptor, binding to RANKL and preventing its interaction with RANK.
RANKL is a member of the TNF, and is essential in osteoclastogenesis. RANKL,
also known as
tumor necrosis factor-related activation-induced cytokine
, osteoprote-
gerin ligand (OPGL), and osteoclast differentiation factor (ODF), is a molecule
participating in bone metabolism. This surface-bound molecule activates osteo-
clasts, cells involved in bone resorption.
RANKL knockout mice exhibit a phenotype of osteopetrosis and defects of tooth
eruption, along with an absence or deficiency of osteoclasts. RANKL activates
NF-
(nuclear factor-kappa B) and NFATc1 (nuclear factor of activated T-cells, cy-
toplasmic, calcineurin-dependent 1) through RANK. NF-
κβ
activation is stimulated
almost immediately after the occurrence of RANKL- RANK interaction, and is not
upregulated. Overproduction of RANKL is implicated in a variety of degenerative
bone diseases, such as rheumatoid arthritis and psoriatic arthritis.
κβ
1.3.5.1
Osteoprotegerin
Cytokines (Greek
cyto
: cell; and
kinos
: movement) are substances (proteins, pepti-
des, or glycoproteins) that are secreted by specific cells of the immune system,
which carry signals between cells, and thus have an effect on other cells. Thus, they
belong to a category of signaling molecules that are used in cellular communication.
The term
cytokine
encompasses a large family of polypeptide regulators that are
widely produced throughout the body by cells of diverse embryological origin.
Researchers in the field of bone biology have, for a long time, sought to
understand the mechanisms responsible for the cross-talk between osteoblasts
and osteoclasts. A major step toward answering this question was provided by the
discovery of OPG. OPG was identified in 1997 by three different groups working
in different areas [170-173].
