Biomedical Engineering Reference
In-Depth Information
Lymphocyte T
RANKL
RANK
OPG
Precursor
of osteoclast
Harmones
cytokines
RANK
Osteoblast
Osteoclast
Bone resorption
Excess of bone
Periodontis
osteoporosis
Figure 1.29
The balance of RANKL and osteoprotegerin
(OPG) controls osteoclast activity. Most (perhaps all) known
inducers of bone resorption and hypercalcemia act indirectly
through the production of RANKL; hence OPG can be used
in pharmacy to control osteoclast activity, independent of
the inducing cytokine. After Stawi nska [189].
produced by preosteoblastic/stromal cells that was both necessary and sufficient for
osteoclast development. The decisive role played by these factors in regulating bone
metabolism was demonstrated by the findings of extremes of skeletal phenotypes
(osteoporosis vs osteopetrosis) in mice [168, 169, 190, 191].
When the rate of bone resorption exceeds that of bone formation, destruction
of bone tissue occurs, resulting in a fragile skeleton. The clinical consequences,
namely, osteoporosis and fragility fractures, are common and costly problems.
Treatments that normalize the balance of bone turnover by inhibiting bone
resorption preserve bone mass and reduce the risk of fracture. The discovery of
RANKL as a pivotal regulator of osteoclast activity provides a new therapeutic target
[171, 192].
Thus, the TNF-family molecule OPGL (also known as
TRANCE
,
RANKL
,and
ODF
) has been identified as a potential ODF and regulator of interactions between
T cells and dendritic cells
in vitro
. OPGL is a key regulator not only of osteo-
clastogenesis but also of lymphocyte development and lymph-node organogenesis
[172-174, 193-195].
Mice belong to a commonly used animal research model with hundreds of
established inbred, outbred, and transgenic strains. Line MC3T3 is a strain of
